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PubMed2002

Conditioning tastant and the acquisition of conditioned taste avoidance to drugs of abuse in DBA/2J mice.

RATIONALE: Conditioned taste aversion (CTA) produced by drugs of abuse such as morphine and cocaine has been interpreted as representing the rewarding actions of these drugs. Evidence for this interpretation is based, in part, on findings in rats indicating saccharin is a more effective conditioning flavor compared to salt (NaCl). However, our studies with ethanol have found salt to be a highly effective conditioning flavor in mice. OBJECTIVES: The present series of studies examined the acquisition of CTA to morphine, ethanol, lithium chloride, and cocaine. Further, saccharin and salt were utilized in each experiment in order to determine effectiveness of each flavor to serve as a conditioning stimulus. METHODS: In four separate experiments, adult male DBA/2J mice were acclimated to a 2 h/day water restriction regimen. Subsequently they received four conditioning trials consisting of 1 h access to either 0.15% w/v saccharin or 0.1 M salt followed by 0, 10 or 20 mg/kg morphine (experiment 1), 0, 2, or 4 g/kg ethanol (experiment 2), 0, 1.5 or 3.0 milliequivalents/kg lithium chloride (experiment 3) or 0, 10 or 20 mg/kg cocaine (experiment 4). A fifth flavor access period (trial 5) was not followed by drug exposure. Following trial 5, each subject received 24-h access to the conditioning flavor and water (two-bottle test 1). Control subjects (0 dose groups from each experiment) received a second two-bottle test with 24-h access to both saccharin and salt flavors. RESULTS: Reduced flavor intake and reduced flavor preference was noted in all drug-paired groups in each experiment. However, more rapid development of CTA was seen with the saccharin flavor in morphine- or cocaine-paired groups. In contrast, ethanol-induced CTA appeared more rapidly with the salt flavor. Lithium-induced CTA was modest, and emerged equally with either flavor. CONCLUSIONS: CTA induced by morphine or cocaine in mice occurs in a similar pattern to that seen in rats, and these findings agree with an interpretation based on drug reward. In contrast, ethanol-induced CTA is more likely attributable to aversive effects.

Animals↗
PubMed2006

Models of metabolic utilization predict limiting conditions for sustained power from conditioned skeletal muscle.

Application and development of muscle powered cardiac assist devices is limited by the ability to predict the sustainable power output of in situ conditioned muscle under the expected loading conditions and geometrical constraints. Empirical definition of the sustained power limits and representative models of the bounding conditions where continuous power can be obtained are needed for device design and optimization. The latissimus dorsi muscles of four goats were chronically conditioned for 11 weeks with an implanted myostimulator. The ability to sustain power under isotonic conditions was evaluated across a range of contraction durations (100-600 ms) and rates (10-120 contractions/min). Muscles were characterized both biomechanically and myothermically to develop and evaluate three increasingly complex empirically-based models of metabolic utilization per contraction based on (1) the duty cycle, (2) a linear function of activation time, and (3) a multivariate-derived function of contraction duration, muscle load, and shortening distance. A clearly defined boundary for sustainable stimulation conditions was observed and was best represented by the linear metabolic model. These data provide both an empirical measure of chronically sustainable muscle power and predictive metabolic models that may be used to optimize the power harnessed for skeletal muscle actuated devices.

Adaptation, Physiological↗
PubMed1995

Conditioned place preferences, conditioned locomotion, and behavioral sensitization occur in rats treated with diethylpropion.

Diethylpropion is a centrally acting appetite-suppressing drug thought to act primarily through catecholamine pathways in the brain. In the present study, four doses of diethylpropion (0, 10, 20, and 40 mg/kg, intraperitoneally) were administered to rats to examine the hypothesis that the drug has psychomotor stimulant properties such as the ability to induce conditioned behaviors and behavioural sensitization. The rats were administered drug and then vehicle on alternating days, and confined to a "drug" or vehicle-paired side of a two-compartment box for 16 pairings. Only the 10-mg/kg dose of diethylpropion increased spontaneous locomotor activity in comparison to vehicle; the 20- and 40-mg/kg doses significantly decreased spontaneous locomotion. All doses of diethylpropion decreased spontaneous rearing, and the 20-and 40-mg/kg doses produced significantly less rearing than the 10-mg/kg one. At the 10-mg/kg dose, conditioned place preferences, conditioned locomotion, and conditioned rearing were observed. The 40-mg/kg dose produced conditioned rearing and conditioned defecation. In response to a 5-mg/kg challenge injection of diethylpropion, behavioural sensitization in locomotion and rearing occurred in rats that had previously received any one of the three doses of diethylpropion. Over 36 days, decreased weight gain was observed only in the 20- and 40-mg/kg groups. The rats were killed 48 h after the last drug injection, and whole brain was analyzed for levels of the catecholamines, homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC), 5-HT (not a catecholamine), and 5-hydroxyindoleacetic acid (5-HIAA) by HPLC with electrochemical detection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2004

Indoor air quality investigation at air-conditioned and non-air-conditioned markets in Hong Kong.

To characterize indoor air quality at the markets in Hong Kong, three non-air-conditioned and two air-conditioned markets were selected for this study. The indoor air pollutants measured included PM(10) (particulate matters with aerodynamic diameter less than 10 microm), total bacteria count (TBC), carbon monoxide (CO), nitric oxide (NO), nitrogen dioxide (NO(2)) and sulfur dioxide (SO(2)). The indoor and outdoor concentrations of these target air pollutants at these markets were measured and compared. The effects of air conditioning, temperature/relative humidity variation and different stalls on the indoor air quality were also investigated. The results indicated that all of the average indoor concentrations of PM(10), TBC, CO and NO(2) at the markets were below the Hong Kong Indoor Air Quality Objectives (HKIAQO) standards with a few exceptions for PM(10) and TBC. The elevated PM(10) concentrations at Hung Hom, Ngau Tau Kok and Wan Chai markets were probably due to the air filtration of outdoor airborne particulates emitted from vehicular exhaust, whereas high concentrations of airborne bacteria at Sai Ying Pun and Tin Shing markets were linked to the use of air conditioning. Correlation analysis demonstrated that indoor bacteria concentrations were correlated with temperature and relative humidity. The operation of air conditioning did not significantly reduce the levels of air pollutants at the markets. However, the higher indoor/outdoor ratios demonstrated that the operation of air conditioning had influence on the levels of bacteria at the markets. It was found that average PM(10) concentration at poultry stalls was higher than the HKIAQO standard of 180 microg/m(3), and was over two times that measured at vegetable, fish and meat stalls. Furthermore, the concentration of airborne bacteria at the poultry stalls was as high as 1031 CFU/m(3), which was above the HKIAQO standard of 1000 CFU/m(3). The bacteria levels at other three stalls were all below the HKIAQO standard. Statistical analysis indicated that there were no significant differences among the four stalls for CO, NO(x) and SO(2).

Air Conditioning↗
PubMed1986

Disruption of neophobia, conditioned odor aversion, and conditioned taste aversion in rats with hippocampal lesions.

Previous studies have implicated the hippocampus in the acquisition of conditioned taste aversions. However, the effect of hippocampal (HPC) lesions on the acquisition of conditioned aversions to the distal olfactory cue has not been investigated. In this study rats with bilateral electrolytic hippocampal lesions were given access to an odor conditioned stimulus (CS) alone or a compound odor-taste CS, followed by an injection of LiCl or saline. The results indicated that HPC lesions attenuated the neophobic response to both CSs, and disrupted conditioned odor and taste aversions, relative to sham-operated controls. Furthermore, the disruption in conditioned odor aversions could not be attributed to attenuation of neophobia in lesioned subjects nor to prolonged neophobia in sham-operated controls. The results are consistent with pharmacological studies in suggesting that the hippocampus is involved in the formation of conditioned odor aversions.

Animals↗
PubMed1988

The effect of lesions of cerebellar cortex on retention of the classically conditioned eyeblink response when stimulation of the lateral reticular nucleus is used as the conditioned stimulus.

Ten male albino rabbits were implanted with stimulating electrodes in the lateral reticular nucleus (LRN). These rabbits were given paired classical conditioning training of the nictitating membrane response with stimulation of the LRN as the conditioned stimulus (CS) Each rabbit was given daily training sessions until it consistently made conditioned responses (CRs). Each rabbit then received an aspiration lesion of cerebellar cortex; the ipsilateral anso-paramedian lobule (n = 6), the anterior or central vermis (n = 2), the central vermis and ansiform lobule (n = 1), or the central vermis and paramedian lobule (n = 1). After recovery, these rabbits were again given paired classical conditioning training with LRN stimulation as the CS. The rabbits with anso-paramedian lesions did not retain the CR after the lesion, but were able to relearn it. The rabbits with lesions of the vermis, the vermis and ansiform, or the vermis and paramedian retained the CR after the lesion. These results are contrasted with previous results, which show that after aspiration of the anso-paramedian lobule, the conditioned response is not retained or relearned when stimulation of the dorsolateral pontine nucleus (DLPN) is used as a CS. The differences between the mossy fiber outputs of the LRN and DLPN may account for this discrepancy. Different regions of the cerebellum are apparently involved in retention of classically conditioned responses depending on the population of mossy fibers carrying the CS information.

Animals↗
PubMed1992

Opponent-process theory and drug conditioning: an assessment for conditioned stimulant-induced movement.

Opponent-process theory occupies an important place in drug conditioning because it accounts for conditioned drug effects which are opposite to those induced by the drug itself. It has not been established, however, whether there is an opponent-process component to stimulant drug induced conditioned effects. In the present study the unilateral 6-hydroxydopamine (6-OHDA) rat model was used to examine this issue. Two groups of Sprague-Dawley rats with equivalent 6-OHDA lesions were administered five apomorphine treatments (0.05 mg/kg s.c.) either paired or unpaired to a 10-min test chamber placement. Apomorphine induced vigorous contralateral rotation and suppressed all ipsilateral rotation. While the apomorphine-induced contralateral rotation response can be conditioned to the test environment cues, the critical test of opponent-process theory in the present study was whether the opposite response of ipsilateral rotation would also become conditioned as a latent opponent-process response to the exteroceptive test environment cues associated with the apomorphine drug state. The postacquisition saline test for conditioning showed that the paired group exhibited higher rates of contralateral and ipsilateral rotation compared to the unpaired group. In addition, when the animals were subsequently tested with the dopaminergic receptor antagonist, haloperidol (0.5 mg/kg), unexpectedly, contralateral rotation was enhanced in the paired group, whereas, ipsilateral rotation was suppressed in both groups. While these findings are, in part, compatible with an opponent-process mechanism, the data supported a simpler explanation; namely, the mechanism of differential habituation in the two groups due to a blocking effect of apomorphine on habituation selectively in the paired group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1998

The effects of hippocampal aspiration lesions on conditioning to the CS and to a background stimulus in trace conditioned suppression.

Rats with hippocampal aspiration lesions or cortical control lesions were compared to sham operated controls in a trace conditioned suppression task, in which a long-lasting background stimulus played the role of more conventional contextual cues. In all three surgical treatment groups, conditioning to the explicit conditioned stimulus (CS) decreased, but conditioning to the background cue increased, when a longer trace interval was used. There was thus no evidence of a differential partitioning of associative conditioning as a result of the lesion, despite the evident sensitivity of the behavioural paradigm to variations in the CS-->unconditioned stimulus (US) interval. This result contrasts with earlier reports using conventional contextual cues in analogous experimental designs, and so suggests that the sensitivity of contextual conditioning to hippocampal dysfunction depends at least in part on the physical nature of conventional contextual cues, and not solely on the less precise predictive information that such cues typically provide.

Animals↗
PubMed1999

Effects of excitotoxic lesions of the basolateral amygdala on conditional discrimination learning with primary and conditioned reinforcement.

Rats with excitotoxic lesions of the basolateral amygdala (BLA) were not impaired in the acquisition of an appetitive visuospatial conditional discrimination between stimuli varying in temporal frequency that has previously been shown to be sensitive to the effects of lesions of the striatum and cingulate cortex. After asymptotic performance was attained, discrimination was reinforced according to a fixed ratio (FR) schedule under which n presentations of sucrose were provided following n correct responses; each correct response also being reinforced immediately by a light acting as a conditioned reinforcer. Under these conditions of reinforcement when FRn=5, BLA-lesioned rats initially showed transient impairments in several aspects of performance, but rapidly attained control levels over subsequent test sessions. No further impairments occurred when FRn=10/20. However, in various conditions of extinction, further differences in performance were revealed between the BLA-lesioned and control groups, notably a significantly enhanced resistance to extinction when both sucrose and conditioned reinforcement were omitted. The results are discussed in terms of limbic-striatal mechanisms in the control of discrimination learning and the possible role of the amygdala in the mediation of different aspects of conditioned reinforcement.

Amygdala↗
PubMed2002

Effect of lesions in the lateral nucleus of the amygdala on fear conditioning using auditory and visual conditioned stimuli in rats.

The lateral nucleus of the amygdala (LA) is believed to be the site of auditory conditioned stimulus (CS) relay in classical fear conditioning. The present study attempts to determine whether the LA is specifically involved in fear conditioning using an auditory CS. Seven rats with lesions in the LA (Tone-Lateral group) and eight sham-operated rats in the control group were trained using an auditory CS (overtone based on an 800 Hz fundamental tone, 70 dB, 3.7 s) paired with foot shock (1.0 mA, 0.5 s). Five rats with lesions in the LA (Light-Lateral group) and eight unoperated rats in the control group were trained using a visual CS (25 W light, 3.7 s). The behavioral index of fear conditioning was a potentiation of the startle reflex in the presence of CS. All rats in the control group and Light-Lateral group showed this potentiation, whereas those in the Tone-Lateral group did not. These results suggest that the LA is an input site of auditory CS information into the amygdala, and that it is not a site of visual CS information input in fear conditioning. Thus, each modality of CS may have a specific subnucleus of the amygdala that mediates fear conditioning.

Acoustic Stimulation↗
PubMed1977

Conditioned stimulus as a determinant of the form of the Pavlovian conditioned response.

The role of the conditioned stimulus (CS) as a determinant of the form of the Pavlovian conditioned response (CR) was investigated in five experiments. Both stabilimeter measures of general activity and detailed observations of the behavior of the rat subjects in the presence of CSs anticipatory to a food unconditioned stimulus (US) were obtained. In Experiment 1, substantially different behaviors to light and tone CSs were observed; further, these differences were found to be dependent on specific learning experience rather than on the mere presence of different stimulation at the time of response evocation. Experiments 2 and 3 investigated the possibility that there was considerable communality of learning to light and tone CSs despite their evoking different CRs. In Experiment 2, prior conditioning of either the tone or light CS was found to block the acquisition of various behaviors to the added element when a light-tone compound stimulus was reinforced, even though the pretrained stimulus did not itself evoke those behaviors. In Experiment 3, the nature of second-order conditioned responding was found to be similar regardless of which first-order CS was used as the reinforcer. Additionally, the reinforcing powers of the light and tone CSs were found to summate. Experiments 4 and 5 examined behaviors to a variety of visual and auditory stimuli paired with food. Stimulus modality and the localizability and vertical location of visual stimuli were found to influence conditioned responding. These results suggested that in this conditioning situation, similar learning of a CS-US relation may be displayed in different overt CRs, depending on the nature of the CS.

Acoustic Stimulation↗
PubMed1979

Effect of posttrial episodes on conditioning in compound conditioned stimuli.

The effect of signaled and nonsignaled posttrial episodes (PTEs) on conditioning to the target CS of a preceding compound CS-US trial was examined in two conditioned emotional response (CER) experiments with rats. Experiment 1 revealed that a nonsignaled PTE, a second shock US, interfered with conditioning to the preceding target CS and that the interference effect of the PTE was greater when it occurred 5 sec as opposed to 1,800 sec after the preceding compound CS-US trial. Experiment 2 revealed that if the shock PTE was signaled by a CS, its ability to interfere with conditioning was reduced. This second study also revealed that omission of an "expected" US interfered with conditioning to the target CS. The implications of these data for information processing models of Pavlovian conditioning are discussed.

Animals↗
PubMed1990

Conditioned responses to a taste conditioned stimulus paired with lithium chloride administration.

The present experiments examined whether behavioral conditioned responses (CRs) develop to lithium chloride (LiCl)-paired tastes and whether these CRs are similar to the behaviors that follow administration of the drug. Rats were exposed to a saccharin solution via intraoral infusions before being injected with either LiCl or saline. CRs were assessed after conditioning when the saccharin conditioned stimulus was delivered alone. The unconditioned response to LiCl delivery is a very distinctive posture that has been termed "lying-on-belly." The present study indicates that this behavior pattern also occurs after the delivery of a LiCl-paired taste solution. The similarity between these unconditioned and conditioned behaviors is consistent with the hypothesis that responses are conditioned during taste aversion acquisition and that CRs are similar to those that are generated by the drugs used in conditioning.

Animals↗
PubMed1991

Conditioned hippocampal cellular response to a behaviorally silent conditioned stimulus.

Multiunit activity (MUA) was chronically recorded in the hippocampal CA3 field of rats using a blocking paradigm with conditioned suppression of lever pressing for food as the measure of conditioning. In Experiment 1, a classical blocking paradigm demonstrated the good conditionability of 2 stimuli (a light and a tone) and their respective ability to block each other. In Experiment 2, MUA was recorded in CA3 cells in rats submitted to a similar paradigm. Four groups received either tone (groups B and B1) or click (groups BC and B1C) conditioned stimulus (CS) presentations that were followed immediately by an electrical footshock (unconditioned stimulus, US). The rats were then given either 40 (groups B and BC) or 1 (groups B1 and B1C) tone + light-footshock presentations. During test sessions, the animals showed MUA responses to the added CS (light), with no conditioned suppression of lever presses occurring during CS presentations. The results of Experiment 3 strongly suggest that hippocampal increase in cellular activity to the light appeared at the first compound trial presentation. Conditioning to the light obtained by increasing the US intensity after the single compound trial suggests that the hippocampal response reflects a redundant CS-US association (light-shock). Long-term retention tests given 45 days after the end of conditioning revealed that behavioral and hippocampal responses could still be detected but only in response to the stimulus that had elicited a behavioral response during learning.

Animals↗
PubMed1995

Lesions of the central nucleus of the amygdala block conditioned excitation, but not conditioned inhibition of fear as measured with the fear-potentiated startle effect.

Lesions of the amygdala block the expression of fear-potentiated startle following either moderate or extensive light + shock training. The present experiment assessed whether lesions of the amygdala would also block the expression of conditioned inhibition of fear. Rats were given conditioned inhibition training in which a light was paired with shock and a noise and light compound was presented in the absence of shock. Then half of the rats were given bilateral electrolytic lesions of the amygdala and the remaining rats were sham operated. Lesions of the amygdala blocked the expression of fear-potentiated startle to the light. To assess whether conditioned inhibition was disrupted, rats were retrained with light + shock pairings with no further conditioned inhibition training. Amygdala lesioned rats reacquired fear-potentiated startle to the light (Kim & Davis, 1993). Importantly, the noise conditioned inhibitor retained its ability to inhibit fear-potentiated startle to the retrained light. These results indicate that areas of the amygdala critical for initial performance of fear-potentiated startle are not critical for the expression of conditioned inhibition.

Amygdala↗
PubMed1997

Lesions of the perirhinal cortex interfere with conditioned excitation but not with conditioned inhibition of fear.

Posttraining lesions of the perirhinal cortex (Prh) have been shown to interfere with the expression of fear. This study assessed whether Prh lesions would also disrupt the inhibition of fear as measured with conditioned inhibition of fear-potentiated startle. Following light + shock, noise-->light-no shock conditioned-inhibition training, rats were given Prh lesions. The lesions interfered with the expression of fear-potentiated startle to the light. To assess whether conditioned inhibition was affected, the rats were given light + retraining without additional noise-->light-training. The noise-conditioned inhibitor retained its ability to inhibit fear-potentiated startle to the retrained light. These results suggest that the areas of the Prh that are essential for the initial expression of conditioned fear are not important for the expression of conditioned inhibition of fear.

Acoustic Stimulation↗
PubMed1998

Ontogenetic differences in the expression of conditioned stimulus conditioning: effects of retention interval.

Preweanling 17-day-old rats were tested for retention of the conditioned emotional response after a 5-min or 24-hr retention interval. For a variety of conditioning parameters (i.e., variation in conditioned stimulus modality, unconditioned stimulus intensity, number of training trials), conditioned responding was consistently weaker after 5 min than after 24 hr. This apparent "incubation," or "hypermnesic," effect was not found in adult rats, even when comparable conditioning levels were indicated on the 24-hr test. The transient short-term retention deficit observed in 17-day-old preweanlings was alleviated by placing the pup in its home cage during the 5-min retention interval or by extending the conditioning session. Fifteen-day-old rat pups did not benefit from home cage exposure or extended training and displayed the transient short-term retention deficit regardless. The results are discussed in terms of age-related effects on time-dependent memory consolidation.

Acoustic Stimulation↗
PubMed1998

Amphetamine-induced conditioned activity is insensitive to perturbations known to affect pavlovian conditioned responses in rats.

Psychostimulant-induced conditioned activity is characterized by the presence of a hyperactivity in drug-free rats exposed to an environment previously paired with the effects of a psychostimulant. This phenomenon is thought to result from a Pavlovian conditioning process. This hypothesis predicts that conditioned activity will be sensitive to perturbations known to affect classical conditioned responses. In direct contrast with this prediction, the authors report here that conditioned activity is insensitive to (a) the temporal order between the stimulant injection and the exposure to the environment, (b) unsignaled stimulant injections between drug-environment pairings, and (c) drug preexposures before the start of drug-environment pairings. It is concluded that the stimulant effects responsible for the establishment of conditioned activity may not be amenable to a Pavlovian associative process.

Amphetamine↗