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PubMed1994

Inhibition of classically conditioned eyeblink responses by stimulation of the cerebellar cortex in the decerebrate cat.

The purpose of the present study was to test the hypothesis that neurones in the anterior interpositus nucleus, under the control of Purkinje cells in the c1 and c3 zones of the cerebellar cortex, exert some control over classically conditioned responses. In particular, the experiments were designed to determine whether the cerebellar control of conditioned and unconditioned responses is different. The experiments were performed on cats decerebrated rostral to the red nucleus under halothane anaesthesia. The cats were conditioned using either a 1000 Hz tone or trains of stimuli through the skin of the proximal forelimb as the conditioned stimulus, and periorbital electrical stimulation as the unconditioned stimulus. A large proportion of the animals acquired conditioned responses at normal rates. It could be shown that these were true conditioned responses and did not result from sensitization or pseudoconditioning. For instance, unpaired presentations of conditioned and unconditioned stimuli caused rapid extinction. Cerebellar areas controlling eyeblink were identified by recording climbing fibre responses in the cerebellar cortex and recording EMG activity in the eyelid evoked by stimulation of the cerebellar cortex. When single shocks of 40-70 microA were applied to these areas during the emission of conditioned eyeblink responses, the latter were strongly inhibited. The inhibition had a latency of about 10 ms and a duration of 25-75 ms. It was shown that this inhibition of the conditioned responses was topographically specific and could only be evoked from cortical sites identified as controlling eyeblink. Stimulation of the periphery of an eyeblink area caused little or no inhibition. The effect of cortical stimulation on unconditioned reflex responses in the orbicularis oculi muscle was also tested. Some inhibition of unconditioned responses was observed, but quantitative analysis showed that this inhibition was considerably weaker than the corresponding inhibition of conditioned responses. The magnitude of the inhibition was determined for unconditioned responses of different sizes including responses which were weaker than the conditioned responses. It is concluded that conditioned eyeblink responses are under strong cerebellar control from areas in the c1 and c3 zones receiving climbing fibre input from the periorbital area. This effect is not likely to be due to a reduction in the background facilitation of facial motoneurones. In contrast, the weak inhibition of the unconditioned response was probably due to this mechanism. The results, therefore, suggest that the conditioned responses are dependent on the cerebellum in a way that is not true of unconditioned responses.

Animals↗

PubMed1997

Contextual conditioned fear blocks the induction but not the maintenance of lateral septal LTP in behaving mice.

High-frequency stimulation (HFS) of the fimbria induces long-term potentiation (LTP) in the lateral septum. This study was aimed at investigating the effect of contextual fear conditioning on septal LTP with the use of behaving C57 BL/6 mice as subjects. For the acquisition of contextual fear conditioning, animals were placed in a conditioning chamber, where they were subjected to footshocks (FSs, 0.6 mA); the following day (retention), animals were reexposed to the chamber. Animals from the first group received HFS in their home cages before being submitted to conditioning; animals from the second group were first submitted to conditioning before receiving HFS during reexposure to the conditioning chamber; animals from the third group were submitted to the same regimen as those from the second group, except that no FS was delivered in the conditioning chamber; and animals from the fourth group received FS in the conditioning chamber but were maintained in their home cages the day after for LTP induction. Before conditioning, animals from the first group, placed in a familiar context (home cage), displayed an LTP of the N3 wave of septal field potential. After conditioning, reexposure of these animals to the conditioning chamber produced a transient decrease in the amplitude of N3 but did not interfere with the duration of maintenance of LTP. Conversely, in animals from the second group, when HFS was applied during reexposure to the conditioning chamber the induction of LTP was totally blocked. However, mice from the two other groups (3rd and 4th) displayed normal levels of LTP. Taken together with previous findings, these data suggest that contextual conditioned fear may interfere with certain forms of learning via blockade of hippocampal-septal LTP.

Animals↗

PubMed2004

Perirhinal cortex supports delay fear conditioning to rat ultrasonic social signals.

Auditory information can reach the lateral nucleus of the amygdala (LA) through a monosynaptic thalamic projection or a polysynaptic cortical route. The polymodal input from the perirhinal cortex (PR) is a major informational gateway to the LA and nearby structures. Pretraining PR lesions impair fear conditioning to a context, but there have been no reports that they cause deficits in delay conditioning to an auditory cue. The direct subcortical projection to the LA seems sufficient to support delay conditioning to a tone conditional stimulus (CS). We examined the effect of PR lesions on delay conditioning to two different tone conditional stimuli (4 and 22 kHz tones; both 10 sec duration) and two different rat ultrasonic vocalization (USV) conditional stimuli (10 sec of "22 kHz USVs"). The two USV conditional stimuli were multi-call segments that were recorded (digitized at 100 kHz) from two different rats. One USV CS was a continuous sequence of eight calls, and the other was a portion of a continuous sequence of six calls. PR lesions significantly impaired conditioning to both USV conditional stimuli and to the training context but had no significant effect on conditioning to either tone CS. The role of PR in fear conditioning appears not to be determined by whether the conditional stimuli serve as contexts or cues, but instead by the nature or complexity of the stimuli or stimulus configurations. These cue-specific effects of PR lesions are suggested to reflect differences in the stimulus features that are encoded in the two CS pathways to the LA.

Acoustic Stimulation↗

PubMed1988

Conditioning of appetitive and consummatory sexual behavior in male Japanese quail.

Two different types of stimulus objects, a live female quail artificially adorned with bright orange feathers and an inanimate toy dog, served as conditioned stimuli. For subjects in experimental groups, the conditioned stimuli were presented shortly before access to a sexually receptive normal female quail. For subjects in control groups, exposure to the conditioned stimuli was unpaired with copulatory opportunity. Subjects in the experimental but not in the control groups quickly came to approach the location of the conditioned stimulus objects. When an adorned female quail served as the conditioned stimulus, the conditioned approach behavior was controlled by a combination of the presence of the orange adornments and the visual cues of the head and neck of the female bird, and the approach behavior persisted as the adorned female moved to new locations. When the toy dog served as the conditioned stimulus, the conditioned approach behavior was limited to the spatial cues that surrounded the toy dog during conditioning trials. Although both types of stimulus objects evoked conditioned approach behavior, only the adorned female stimulus supported copulatory behavior. This last finding indicates that copulatory behavior can become redirected toward novel stimuli as a result of conditioning, but only under special circumstances. The results are consistent with the suggestion that appetitive components of reproductive behavior are more susceptible to conditioning than consummatory components. Possible reasons for this are discussed, together with implications of the results for the contribution of conditioning processes to sexual selection.

Animals↗

PubMed1984

Acquisition and extinction of conditioned suppression of a graft-vs-host response in the rat.

Injection of rats with cyclophosphamide (CY) after their consumption of a novel saccharin-flavored drinking solution results in a conditioned aversion to saccharin and a conditioned suppression of immune responses. In this study, female Lewis X Brown Norwegian F1 rats were conditioned by pairing saccharin with 50 mg/kg CY. Seven weeks later (day 0), a graft-vs-host response (GvHR) was induced in these animals by injecting splenic leukocytes from Lewis donors into a rear footpad. At this time, some conditioned animals were reexposed to saccharin, the conditioned stimulus. During the 7-wk interval between conditioning and immunization, subgroups of conditioned rats were given 0, 4, 9, or 18 extinction trials (saccharin followed by saline injections). Animals receiving 4, 9, or 18 extinction trials showed a greater preference for saccharin on day 0 than did animals receiving no extinction trials, but these groups did not differ among themselves; all conditioned groups showed a lower preference for saccharin than placebo-treated animals. There was a clear effect of number of extinction trials on the GvHR. Animals receiving 9 or 18 extinction trials did not differ from controls, whereas animals receiving 0 or 4 trials had a milder GvHR than did conditioned rats that were not reexposed to saccharin at the time of immunization. These results confirm a previous report of conditioned suppression of a GvHR, demonstrate that conditioned immunopharmacologic responses are subject to experimental extinction, and indicate that conditioned immunosuppression can be dissociated from conditioned taste aversion.

Animals↗

PubMed1998

Phosphorylation of mitogen-activated protein kinase by one-trial and multi-trial classical conditioning.

The pathway supporting the conditioned stimulus (CS) is one site of plasticity that has been studied extensively in conditioned Hermissenda. Several signal transduction pathways have been implicated in classical conditioning of this preparation, although the major emphasis has been on protein kinase C. Here we provide evidence for the activation and phosphorylation of a mitogen-activated protein kinase (MAPK) pathway by one-trial and multi-trial conditioning. A one-trial in vitro conditioning procedure consisting of light (CS) paired with the application of 5-HT results in the increased incorporation of 32PO4 into proteins detected with two-dimensional gel electrophoresis. Two of the phosphoproteins have molecular weights of 44 and 42 kDa, consistent with extracellular signal-regulated protein kinases (ERK1 and ERK2). Phosphorylation of the 44 and 42 kDa proteins by one-trial conditioning was inhibited by pretreatment with PD098059, A MEK1 (ERK-Activating kinase) inhibitor. Assays of ERK activity with brain myelin basic protein as a substrate revealed greater ERK activity for the group that received one-trial conditioning compared with an unpaired control group. Western blot analysis of phosphorylated ERK using antibodies recognizing the dually phosphorylated forms of ERK1 and ERK2 showed an increase in phosphorylation after one-trial conditioning compared with unpaired controls. The increased phosphorylation of ERK after one-trial conditioning was blocked by pretreatment with PD098059. Hermissenda that received 10 or 15 conditioning trials showed significant behavioral suppression compared with pseudo-random controls. After conditioning and behavioral testing, the conditioned animals showed significantly greater phosphorylation of ERK compared with the pseudo-random controls. These results show that the ERK-MAPK signaling pathway is activated in Pavlovian conditioning of Hermissenda.

Animals↗

PubMed2007

Conditioning on the propensity score can result in biased estimation of common measures of treatment effect: a Monte Carlo study.

Propensity score methods are increasingly being used to estimate causal treatment effects in the medical literature. Conditioning on the propensity score results in unbiased estimation of the expected difference in observed responses to two treatments. The degree to which conditioning on the propensity score introduces bias into the estimation of the conditional odds ratio or conditional hazard ratio, which are frequently used as measures of treatment effect in observational studies, has not been extensively studied. We conducted Monte Carlo simulations to determine the degree to which propensity score matching, stratification on the quintiles of the propensity score, and covariate adjustment using the propensity score result in biased estimation of conditional odds ratios, hazard ratios, and rate ratios. We found that conditioning on the propensity score resulted in biased estimation of the true conditional odds ratio and the true conditional hazard ratio. In all scenarios examined, treatment effects were biased towards the null treatment effect. However, conditioning on the propensity score did not result in biased estimation of the true conditional rate ratio. In contrast, conventional regression methods allowed unbiased estimation of the true conditional treatment effect when all variables associated with the outcome were included in the regression model. The observed bias in propensity score methods is due to the fact that regression models allow one to estimate conditional treatment effects, whereas propensity score methods allow one to estimate marginal treatment effects. In several settings with non-linear treatment effects, marginal and conditional treatment effects do not coincide.

Bias↗

PubMed2005

Classical conditioning of endocrine effects.

PURPOSE OF REVIEW: Classical conditioning is a form of associative learning, based on the pioneering work of I. P. Pavlov: due to its association with an unconditioned stimulus that induces an unconditioned response, an initially neutral stimulus will become a conditioned stimulus evoking a conditioned response in the absence of the unconditioned stimulus. One important area for the application of conditioning principles is the regulation of physiological systems in general, and endocrine responses and its concomitant changes specifically. Conditioned endocrine responses were predominantly addressed in animal studies so far, mainly examining conditioned insulin production (and blood-glucose change) and corticosterone release. RECENT FINDINGS: There are very few studies on classical conditioning of endocrine responses in the annual period of this review. The advancement, however, is that some are conducted with humans. Recently, as a new avenue, hormones and neurotransmitters have been examined as mediators of basic conditioning processes. Moreover, there is an increasing interest in gender-specific conditioning responses which are influenced by gonadal hormones. SUMMARY: Research on classical conditioning demonstrates that endocrine systems are adaptable to environmental signals. Likewise, the endocrine status of an organism (at least with regard to glucocorticoids and gonadal hormones) was shown to modify classically conditioned responses. Partly due to the high expenditure of conducting conditioning experiments, the quantity of studies is limited, but there is a need to extend this research to humans. In sum, the application of conditioning paradigms constitutes an important research tool for behavioral medicine as well as psychiatry to examine brain-behavior relationships.

Journal Article↗

PubMed2002

The medical condition regard scale: measuring reactions to diagnoses.

PURPOSE: To develop a non-condition-specific scale to capture biases, emotions, and expectations generated by medical condition descriptors. METHOD: An 18-item pilot scale was developed from the literature on physicians' responses to patients they like and dislike, stigma definitions, and discussions with primary care faculty. Exploratory factor analysis was conducted after 440 medical students rated one of 12 diverse conditions. Confirmatory factor analysis was performed after 163 medical students rated two psychiatric conditions. Validity was evaluated by the scale's ability to meaningfully stratify the 12 conditions and identify changes in attitudes toward psychiatric conditions after a psychiatry clerkship. RESULTS: Exploratory factor analysis supported an 11-item unidimensional solution (all factor loadings >.40, coefficient alpha =.87). The final scale, the Medical Condition Regard Scale (MCRS), taps the degree to which medical students find patients with a given medical condition to be enjoyable, treatable, and worthy of medical resources. The unidimensional model also was supported by the confirmatory factor analyses for the two psychiatric conditions (both comparative fit indices =.98). The scale stratified the 12 conditions as expected: straightforward medical conditions rated highest, somatoform conditions rated lowest. Students showed greater regard for patients with major depression after the psychiatry clerkship, and students who rotated through an addiction treatment program showed a greater increase in regard for patients with alcoholism than did students not exposed to addiction treatment. CONCLUSION: MCRS scores are reliable, and the scale appears to be a valid instrument for assessing regard for any medical condition.

Adult↗

PubMed1990

Conditioned taste aversion and motion sickness in cats and squirrel monkeys.

The relationship between vomiting and conditioned taste aversion was studied in intact cats and squirrel monkeys and in cats and squirrel monkeys in which the area postrema was ablated by thermal cautery. In cats conditioned 7-12 months after ablation of the area postrema, three successive treatments with xylazine failed to produce either vomiting or conditioned taste aversion to a novel fluid. Intact cats, however, vomited and formed a conditioned aversion. In squirrel monkeys conditioned 6 months after ablation of the area postrema, three treatments with lithium chloride failed to produce conditioned taste aversion. Intact monkeys did condition with these treatments. Neither intact nor ablated monkeys vomited or evidenced other signs of illness when injected with lithium chloride. When the same ablated cats and monkeys were exposed to a form of motion that produced vomiting prior to surgery, conditioned taste aversion was produced and some animals vomited. These findings confirm other studies indicating motion can produce vomiting in animals with the area postrema destroyed and demonstrate that motion-induced conditioned taste aversion can be produced after ablation of the area postrema. The utility of conditioned taste aversion as a measure of subemetic motion sickness is discussed by examining agreement and disagreement between identifications of motion sickness by conditioned taste aversion and vomiting. It is suggested that a convincing demonstration of the utility of conditioned taste aversion as a measure of nausea requires the identification of physiological correlates of nausea, and caution should be exercised when attempting to interpret conditioned taste aversion as a measure of nausea.

Animals↗

PubMed2004

Health-related quality of life among adolescents with allergy-like conditions - with emphasis on food hypersensitivity.

BACKGROUND: It is known that there is an increase in the prevalence of allergy and that allergic diseases have a negative impact on individuals' health-related quality of life (HRQL). However, research in this field is mainly focused on individuals with verified allergy, i.e. leaving out those with self-reported allergy-like conditions but with no doctor-diagnosis. Furthermore, studies on food hypersensitivity and quality of life are scarce. In order to receive information about the extent to which adolescent females and males experience allergy-like conditions and the impact of these conditions on their everyday life, the present study aimed to investigate the magnitude of self-reported allergy-like conditions in adolescence and to evaluate their HRQL. Special focus was put on food hypersensitivity as a specific allergy-like condition and on gender differences. METHODS: In connection with lessons completed at the children's school, a study-specific questionnaire and the generic instrument SF-36 were distributed to 1488 adolescents, 13-21 years old (response rate 97%). RESULTS: Sixty-four per cent of the respondents reported some kind of allergy-like condition: 46% reported hypersensitivity to defined substances and 51% reported allergic diseases (i.e. asthma/wheezing, eczema/rash, rhino-conjunctivitis). A total of 19% reported food hypersensitivity. Females more often reported allergy-like conditions compared with males (p < 0.001). The adolescents with allergy-like conditions reported significantly lower HRQL (p < 0.001) in seven of the eight SF-36 health scales compared with adolescents without such conditions, regardless of whether the condition had been doctor-diagnosed or not. Most adolescents suffered from complex allergy-like conditions. CONCLUSIONS: The results indicate a need to consider the psychosocial impact of allergy-like conditions during school age. Further research is needed to elucidate the gender differences in this area. A team approach addressing better understanding of how allergy-like conditions impair the HRQL may improve the management of the adolescent's health problems, both in health-care services and in schools.

Adolescent↗

PubMed2000

Pest control by the introduction of a conditional lethal trait on multiple loci: potential, limitations, and optimal strategies.

Advances in genetics have made it feasible to genetically engineer insect strains carrying a conditional lethal trait on multiple loci. We model the release into a target pest population of insects carrying a dominant and fully penetrant conditional lethal trait on 1-20 loci. Delaying the lethality for several generations after release allows the trait to become widely spread in the target population before being activated. To determine effectiveness and optimal strategies for such releases, we vary release size, number of generations until the conditional lethality, nonconditional fitness cost resulting from gene insertions, and fitness reduction associated with laboratory rearing. We show that conditional lethal releases are potentially orders of magnitude more effective than sterile male releases of equal size, and that far smaller release sizes may be required for this approach than necessary with sterile males. For example, a release of male insects carrying a conditional lethal allele that is activated in the F4 generation on 10 loci reduces the target populatioin to 10(-4) of no-release size if there are initially two released males for every wild male. We show how the effectiveness of conditional lethal releases decreases as the nonconditional fitness reduction (i.e., fitness reduction before the trait becomes lethal) associated with the conditional lethal genes increases. For example, if there is a 5% nonconditional fitness cost per conditional lethal allele, then a 2:1 (released male:wild male) release with conditional lethal alleles that are activated in the F4 generation reduces the population to 2-5% (depending on the degree of density dependence) of the no-release size. If there is a per-allele reduction in fitness, then as the number of loci is increased there is a trade-off between the fraction of offspring carrying at least one conditional lethal allele and the fitness of the released insects. We calculate the optimal number of loci on which to insert the conditional lethal gene given various conditions. In addition, we show how laboratory-rearing fitness costs, density-dependence, and all-male versus male-female releases affect the efficiency of conditional lethal releases.

Alleles↗

PubMed1994

Principal descriptors of body condition score in Holstein cows.

The objective of this study was to assess objectively the ability of observers to assess body condition of dairy cows. Four observers independently assigned a body condition score (five-point scale, .25 increments) and described the appearance of seven body regions of 225 Holstein cows. Areas described were the thurl region, ischial and ileal tuberosities, ilio-sacral and ischio-coccygeal ligaments, transverse processes of the lumbar vertebrae, and spinous processes of the lumbar vertebrae. An absolute body condition score was designated for each cow based on the modal body condition score for all observers. If there was no modal body condition score, the mean score was used for the absolute body condition score. Statistical analysis of principal components was used to examine the relationship between body region description and absolute body condition score. Descriptions of body regions were highly correlated across all absolute body condition scores. Four principal component vectors explained 83.6% of the variation of the body region correlation matrix. The first principal latent vector accounted for 55% of the variation and was uniformly correlated with all body regions. Analysis of variance of first principal latent vector as the dependent variable and absolute body condition score as the class variable indicated that body condition could be separated into .25 units between 2.5 and 4.0, inclusively. Below 2.5 and > 4.0, body condition could only be separated by .5 units. Distinct changes in specific body regions were associated with change in absolute body condition score. Observers agreed with the absolute score 58.1% of the time, deviating by .25 units 32.6% of the time. A body condition score can be given to a cow based on principal descriptors of specific body regions between 2.5 and 4.0 by .25 units.

Adipose Tissue↗

PubMed1997

Conditioning injuries associated with artificial turf in two preseason football training programs.

OBJECTIVE: To compare the occurrence of preseason football conditioning injuries in traditional and crossover conditioning programs over five preseasons. DESIGN AND SETTING: The turf group performed all preseason conditioning by running or sprinting on artificial turf, and the turf and swim group alternated all preseason conditioning by running and sprinting on artificial turf or kickboard swimming. SUBJECTS: Subjects were 519 NCAA Division III physically active football players. MEASUREMENTS: Previous conditioning injuries, preseason conditioning injuries, missed practices, and missed conditioning sessions were recorded. Exact numbers and areas of injury for each year and each group were tabulated. A chi-square statistic compared the two groups and a logistic regression model was used to estimate the risk of becoming injured and the types of conditioning injuries experienced in the two groups. RESULTS: Prevalence of injury was significantly different in the two groups. In the turf group, 35% of subjects developed a conditioning injury; in the turf and swim group, 13% developed a conditioning injury (x(2)= 33.16, p <.0001). No significant difference in missed practices or missed conditioning sessions was found. CONCLUSIONS: The turf and swim group experienced significantly fewer football preseason conditioning injuries than the turf group. The crossover effects of a running and swimming program may decrease the number of overuse injuries associated with repetitive running on artificial turf in traditional preseason conditioning programs.

Journal Article↗

PubMed1986

Effects of interstimulus interval and contingency on classical conditioning of the Aplysia siphon withdrawal reflex.

The siphon withdrawal reflex of Aplysia undergoes differential classical conditioning with cutaneous stimulation of the siphon or mantle shelf as the discriminative conditioned stimuli (CS+ and CS-) and shock to the tail as the unconditioned stimulus (US). The reflex has proved to be useful for analyzing the neural mechanisms of conditioning. To test the generality of this experimental system, we have begun to compare the properties of conditioning in Aplysia with those of conditioning in vertebrates. We first examined the effect of the interstimulus interval (ISI) by varying the time between presentation of the CS+ and the US in different groups of animals. Significant differential conditioning was obtained when the onset of the CS+ preceded the onset of the US by 0.5 sec, and marginal conditioning was obtained when the ISI was 1.0 sec. By contrast, no significant conditioning occurred when the CS+ preceded the US by 2, 5, or 10 sec, when the onsets of the stimuli were simultaneous, or when US onset preceded the CS+ by 0.5, 1.0, or 1.5 sec (backward conditioning). We next examined the effect of contingency by giving one group of animals normal differential conditioning, and a second group the same training but with additional USs inserted between the paired trials. Presentation of these additional USs reduced the degree to which the US was contingent on the CS+, but did not change the number of pairings. Animals receiving normal training again showed significant conditioning, whereas animals receiving additional USs showed no conditioning.(ABSTRACT TRUNCATED AT 250 WORDS)

Aplysia↗

PubMed1994

Effect of conditioning with d-amphetamine on the extracellular concentration of dopamine and its metabolites in the striatum of behaving rats.

The effect of classical conditioning with d-amphetamine on the extracellular concentrations of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum of awake, freely moving rats was studied using microdialysis. This was done in order to test, whether there occurred alterations in DA release as conditioned responses in the striatum. The first series of experiments studied the acute effects of d-amphetamine on the concentration of DA and its metabolites DOPAC and HVA. d-Amphetamine (2 mg/kg, s.c.) increased extracellular DA and decreased DOPAC and HVA. Behaviorally, it led to stereotyped locomotor activation and sniffing. In principle, these observations confirmed earlier findings. In a second series, conditioned responses to d-amphetamine were studied. Rats were implanted with guide cannulas prior conditioning experiments started. For conditioning experiments, the rats were divided into three groups: conditioned group, pseudoconditioned group and a drug-naive control group. After 7 daily training sessions with d-amphetamine (2 mg/kg), on the 8th day, the test day, rats were injected with saline and exposed to the conditional stimuli, while they were observed for their stereotyped, conditioned response. Additionally, microdialysis was performed in order to observe possible changes in the extracellular transmitter or metabolite concentrations. Conditioning with amphetamine led to conditioned stereotypic behavior. In comparison with the pseudoconditioned rats, there was an increase in DA release as conditioned response to amphetamine. In pseudoconditioned rats. DOPAC and HVA were slightly higher than in both other groups. DOPAC and HVA were lower in rats conditioned to d-amphetamine when compared with the pseudoconditioned ones.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

PubMed2004

Effects of corticosterone on place conditioning to ethanol.

RATIONALE AND OBJECTIVE: Effects of corticosterone on place conditioning to ethanol were investigated in mice using two conditioning schedules; the conventional method and a rapid conditioning schedule in which exposure to the CS+ followed immediately on exposure to the CS-. METHODS: Effects of administration of corticosterone, 10 mg/kg, on the acquisition of place conditioning produced by ethanol, 1-2.5 g/kg, were investigated using the conventional method of conditioning, with exposure to the CS+ and the CS- on alternate days, and also using the rapid conditioning method. Total and free blood corticosterone concentrations were measured after administration of ethanol and corticosterone. RESULTS: In the conventional, alternate day, conditioning schedule, ethanol produced significant place preference at 2 and at 2.5 g/kg, but when these alcohol doses were given with corticosterone 10 mg/kg, significant place conditioning was not seen. In contrast, in the rapid, same day, conditioning schedule corticosterone significantly decreased the dose at which ethanol produced an apparent place preference, with significant place conditioning being seen with ethanol at 1 and 1.5 g/kg in combination with corticosterone, 10 mg/kg. Total and free corticosterone concentrations were increased after ethanol, 1.5 g/kg, compared with controls, and administration of corticosterone, 10 mg/kg, caused a significantly greater increase. There were no significant differences in spontaneous locomotor activity or brain alcohol concentrations between any of the treatment groups. CONCLUSIONS: The effects of corticosterone on ethanol-induced place conditioning are substantially affected by the conditioning schedule used.

Animals↗

PubMed2007

Conditioned effects of heroin on the expression of inducible nitric oxide synthase in the rat are susceptible to extinction and latent inhibition.

RATIONALE: The administration of heroin has been shown to inhibit the induction of nitric oxide, a molecule known to play a critical role in immune function. Previous research has shown that this alteration can be conditioned to environmental stimuli that have been associated with drug administration. However, it remains unknown whether the conditioned effects of heroin on nitric oxide formation follow accepted principles of learning. OBJECTIVE: This study sought to determine whether manipulations that induce extinction and latent inhibition, two learning paradigms known to reduce the expression of conditioned responses, would alter heroin's conditioned effects on the expression of inducible nitric oxide synthase (iNOS). MATERIALS AND METHODS: The conditioning procedure involved repeated pairing of heroin administration with placement into a standard conditioning chamber. Rats were repeatedly exposed to the chambers without heroin reinforcement to determine whether the conditioned response would extinguish. To induce latent inhibition, rats received repeated exposure to the chamber before the start of conditioning to inhibit the acquisition of the conditioned response. Ten days after the final conditioning session, all rats were injected with lipopolysaccharide (LPS) to induce iNOS expression. Spleen and liver tissue were removed to determine iNOS expression using reverse transcriptase polymerase chain reaction. Blood was collected to determine the concentration of nitrite/nitrate. RESULTS: The results showed that both extinction and latent inhibition reduced the conditioned effects of heroin on the production of nitric oxide. CONCLUSION: This study provides the first evidence that the conditioned effects of heroin on nitric oxide production follow accepted principles of learning.

Animals↗