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Cocaine-induced conditioned taste avoidance over extended conditioned stimulus-unconditioned stimulus intervals.

Although long-delay learning has been demonstrated numerous times in the conditioned taste avoidance procedure, the empirical evidence showing this is almost exclusively limited to studies using emetics. Given that compounds outside the emetic class (e.g. drugs of abuse) are also effective in inducing conditioned taste avoidances, the present study assessed the ability of cocaine, a non-emetic psychoactive compound, to support long-delay conditioning as the unconditioned stimulus in conditioned taste avoidance preparation. Using saccharin as the conditioned stimulus, two taste-drug pairings were followed by six extinction trials during which saccharin was presented without subsequent injections of cocaine. During the two conditioning trials, animals were injected subcutaneously with cocaine (32 mg/kg) at different conditioned stimulus-unconditioned stimulus intervals, that is, 10, 60, 120, 180, 240, 300, 420 and 540 min. A control group of animals was given an equi-volume injection of the drug vehicle at the 10-min conditioned stimulus-unconditioned stimulus interval. After two conditioning trials, all treatment groups consumed significantly less saccharin than controls, with the magnitude of the effect decreasing as the conditioned stimulus-unconditioned stimulus interval increased. After six extinction trials, animals injected with cocaine at 10, 60 and 120 min conditioned stimulus-unconditioned stimulus intervals still consumed significantly less than controls. These results with cocaine suggest that taste avoidance learning over long delays is not limited to classical emetic compounds and may, in fact, be characteristic of taste avoidance learning in general.

Animals↗

Deriving utility scores for co-morbid conditions: a test of the multiplicative model for combining individual condition scores.

BACKGROUND: The co-morbidity of health conditions is becoming a significant health issue, particularly as populations age, and presents important methodological challenges for population health research. For example, the calculation of summary measures of population health (SMPH) can be compromised if co-morbidity is not taken into account. One popular co-morbidity adjustment used in SMPH computations relies on a straightforward multiplicative combination of the severity weights for the individual conditions involved. While the convenience and simplicity of the multiplicative model are attractive, its appropriateness has yet to be formally tested. The primary objective of the current study was therefore to examine the empirical evidence in support of this approach. METHODS: The present study drew on information on the prevalence of chronic conditions and a utility-based measure of health-related quality of life (HRQoL), namely the Health Utilities Index Mark 3 (HUI3), available from Cycle 1.1 of the Canadian Community Health Survey (CCHS; 2000-01). Average HUI3 scores were computed for both single and co-morbid conditions, and were also purified by statistically removing the loss of functional health due to health problems other than the chronic conditions reported. The co-morbidity rule was specified as a multiplicative combination of the purified average observed HUI3 utility scores for the individual conditions involved, with the addition of a synergy coefficient s for capturing any interaction between the conditions not explained by the product of their utilities. The fit of the model to the purified average observed utilities for the co-morbid conditions was optimized using ordinary least squares regression to estimate s. Replicability of the results was assessed by applying the method to triple co-morbidities from the CCHS cycle 1.1 database, as well as to double and triple co-morbidities from cycle 2.1 of the CCHS (2003-04). RESULTS: Model fit was optimized at s = .99 (i.e., essentially a straightforward multiplicative model). These results were closely replicated with triple co-morbidities reported on CCHS 2000-01, as well as with double and triple co-morbidities reported on CCHS 2003-04. CONCLUSION: The findings support the simple multiplicative model for computing utilities for co-morbid conditions from the utilities for the individual conditions involved. Future work using a wider variety of conditions and data sources could serve to further evaluate and refine the approach.

Journal Article↗

[Relationship between body condition (back fat thickness and body condition scoring) and fertility in dairy cows (German Black Pied/HF)].

It was the aim of this study to compare body condition scoring with ultrasonographic back fat thickness. Additionally, the relationship between back fat thickness and fertility, milk yield, number of parity and stage of lactation in dairy cows was examined. Body condition of 211 cows (German Black Pied/HF) was determined by means of ultrasonographic back fat thickness (BFT) and body condition scoring (BCS). The BFT and the BCS were measured at four different stages during the course of lactation (Time point 1 (T1) = 1.-3. d postpartum (pp); T2 = 40.-42. d pp; T3 = 90.-92. d pp and T4 = 130.-150. d pp). Number of parity, 100-day-milk-yield, incidence of ovarian cysts, incidence of acyclicity and fertility measures were recorded. There was a significant correlation between body condition scoring and ultrasonographic measurement of back fat thickness at the four time points (r = 0.68 to 0.74). Therefore, both methods were suitable to evaluate body condition. The number of lactations had an influence on body condition. At T1, the BFT in older cows was significantly higher than in younger cows (P < 0.05). At T3, the BFT in younger cows was higher than in older cows (P < 0.05). With regards to the stage of lactation, there was a significant decrease in body condition from T1 to T2 and T3. At T4, body condition increased, but did not reach the level of the postcalving values. In addition, cows with a high BFT at the beginning of lactation had a higher milk yield and a higher loss of body fat than cows with lower milk yield. Heifers compensated this loss of body fat significantly faster than older cows. Particularly at T3, body condition had an impact on fertility. Cows with a high loss of body condition between T1 and T3 developed significantly more often ovarian cysts than cows with low loss of back fat thickness. Cows with the lowest BFT at T3 had the longest calving to first service intervall and the highest 200-day-non-pregnancy index. In conclusion, our results suggest that there might be a certain relationship between body condition and fertility (delayed first service, ovarian disorders, reduced pregnancy results).

Adipose Tissue↗

Classical conditioning in the rat fetus. III. Retention, extinction, and re-activation of the conditioned response (CR).

A single paired presentation of an artificial nipple (conditioned stimulus, CS) and milk (unconditioned stimulus, US) resulted in classical conditioning. When re-exposed to the artificial nipple CS after conditioning, fetuses showed fewer oral grasp responses compared to control fetuses exposed to the milk (US) and artificial nipple (CS) in an unpaired fashion. The reduction in oral grasping was evident when the test of oral grasping was administered 18 min after conditioning but not 21 to 30 min after conditioning (Experiments 1a and 1b). Experiments 2a and 2b confirmed that nine or more exposures to the CS after conditioning, without a milk infusion, resulted in experimental extinction of the conditioned reduction in oral grasping. One re-exposure to milk during the period after classical conditioning was sufficient to re-activate memory for the association between artificial nipple CS and milk US (Experiment 3a). Fetuses exposed to one or two re-activation treatments that comprised an intraoral infusion of milk showed evidence of the conditioned reduction in oral grasping when tested after a delay sufficient to produce forgetting. Experiment 3b showed that the orosensory properties of milk were sufficient to re-activate fetal memory for the association between artificial nipple and milk. Experiment 3c indicated that central injection of 10 ng of dynorphin A 1-13 re-activated fetal memory for the classically conditioned association. Experiments 3b and 3c suggested that the orosensory properties of milk activated a kappa opioid system in the fetal brain that reduced oral grasping of the artificial nipple during the test for oral grasping.

Animals↗

Dose- and conditioning trial-dependent ethanol-induced conditioned place preference in Swiss-Webster mice.

The motivational effects of ethanol were examined in Swiss-Webster mice using an unbiased place conditioning, design. Adult male Swiss-Webster mice received six 5-min pairings of a tactile stimulus with different doses of ethanol (1, 2, 3, or 4 g/kg. IP). A different tactile stimulus was paired with saline injections. A 60-min preference test was given after the first four conditioning trials and an additional 30-min preference test after the sixth conditioning trial. During conditioning, ethanol initially produced locomotor stimulation at the 2 g/kg dose and locomotor depression at the 4 g/kg dose. However, after repeated ethanol exposure, all doses produced overall increases in activity relative to saline, suggesting sensitization to ethanol's stimulant effect. After four conditioning trials ethanol-induced conditioned place preference was noted in mice receiving 3 and 4 g/kg ethanol. After two additional conditioning trials all ethanol doses produced conditioned place preference. These results indicate that ethanol has dose-dependent rewarding effects measured in an unbiased place-conditioning paradigm using a standard outbred mouse strain. Further, additional place-conditioning trials enhance the development of preference at lower (1 or 2 g/kg) ethanol doses.

Animals↗

Effects of potentially phobic conditioned stimuli on retention, reconditioning, and extinction of the conditioned skin conductance response.

Discriminative classical conditioning of skin conductance responses (SCRs) was studied in 163 college students as a function of four variables: CS type (potentially phobic versus neutral conditioned stimuli), Sex of the subject, Interstimulus interval (ISI) during conditioning (.5 versus 8 s), and Retention interval between conditioning and retention assessment (1 versus 6 months). CS type did not affect acquisition, retention, or reconditioning of the differential conditioned responses. The effect of CS type was highly significant during extinction, with differential SCRs to CS+ and CS- being greater with potentially phobic conditioned stimuli. This was true for both sexes, both the .5-s and the 8-s ISI, and after a 1-month or a 6-month retention interval. Moreover, SCRs conditioned to phobic conditioned stimuli with the .5-s ISI persisted even after subjects' cognitive expectancy of the UCS, which was measured on a trial-by-trial basis, had completely extinguished. The results indicate that the effect of potentially phobic conditioned stimuli on the conditioned skin conductance response is unique to resistance to extinction-they affect not learning but unlearning of the autonomic response.

Adult↗

Immune enhancement by conditioning of senescent mice. Comparison of old and young mice in learning ability and in ability to increase natural killer cell activity and other host defense reactions in response to a conditioned stimulus.

It has been clearly demonstrated that immune responses may be conditioned in a manner similar to that of the classical Pavlovian experiments. Evidence of impaired immune function in aging has raised the question of whether psychological conditioning of an immune response can also be effective in old age. The knowledge that aged mice have decreased spleen cell natural killer (NK) activity and that NK cytotoxicity, at least in young mice, can be psychologically conditioned led us to explore in old mice the possibility of conditioning the response of NK cell activity using the odor of camphor as the conditioned stimulus (CS) and the injection of Poly I:C as the unconditioned stimulus (US). Young and old male mice were divided into five and six groups, respectively. They received the CS and/or the US in association (conditioning) trials (sessions 1-9). Mice were exposed to the camphor odor alone at 72 hours after the final association trial to observe the conditioning phenomenon (session 10). The group conditioned with Poly I:C and camphor and receiving the CS at session 10 showed statistically significant increases in spleen cell NK activity over those of the control groups that did not receive the CS treatment at session 10 (2.6- and 4.0-fold increase in young and old, respectively). Treatment with camphor odor alone had no effect on boosting NK cell activity. These findings demonstrate the possibility of conditioning immune responses in old age, offering a valuable tool for attenuating age-related immune deterioration in various species, including the human. In addition, these results again confirm highly significant immune enhancement by classical conditioning and extend previous findings from female mice to males as well.

Aging↗

Inhibition of conditioned stimulus pathway phosphoprotein 24 expression blocks the reduction in A-type transient K+ current produced by one-trial in vitro conditioning of Hermissenda.

Long-term intrinsic enhanced excitability is a characteristic of cellular plasticity and learning-dependent modifications in the activity of neural networks. The regulation of voltage-dependent K+ channels by phosphorylation/dephosphorylation and their localization is proposed to be important in the control of cellular plasticity. One-trial conditioning in Hermissenda results in enhanced excitability in sensory neurons, type B photoreceptors, of the conditioned stimulus pathway. Conditioning also regulates the phosphorylation of conditioned stimulus pathway phosphoprotein 24 (Csp24), a cytoskeletal-related protein containing multiple beta-thymosin-like domains. Recently, it was shown that the downregulation of Csp24 expression mediated by an antisense oligonucleotide blocked the development of enhanced excitability in identified type B photoreceptors after one-trial conditioning without affecting short-term excitability. Here, we show using whole-cell patch recordings that one-trial in vitro conditioning applied to isolated photoreceptors produces a significant reduction in the amplitude of the A-type transient K+ current (I(A)) detected 1.5-16 h after conditioning. One-trial conditioning produced a depolarized shift in the steady-state activation curve of I(A) without altering the inactivation curve. The conditioning-dependent reduction in I(A) was blocked by preincubation of the photoreceptors with Csp antisense oligonucleotide. These results provide an important link between Csp24, a cytoskeletal protein, and regulation of voltage-gated ion channels associated with intrinsic enhanced excitability underlying pavlovian conditioning.

Analysis of Variance↗

Conditioned reinforcement by conditional discriminative stimuli.

A concurrent-chains schedule was used to examine how a delay to conditional discriminative stimuli affects conditioned reinforcement strength. Pigeons' key-peck responses in the initial link produced either of two terminal links according to independent variable-interval 30-s schedules. Each terminal link involved an identical successive conditional discrimination and was segmented into three links: a delay interval (green), a color conditional discriminative stimulus (blue or red), and a line conditional discriminative stimulus (vertical or horizontal lines). Food delivery occurred 45 s after entering the terminal link with a probability of .5, but its conditional probability (1.0 or 0) depended on the combination of the color and the line stimuli. One of the color stimuli occurred independently of further responding, 5 s after entry into the right terminal link, but it occurred 35 s after entry into the left terminal link. One of the line stimuli occurred independently of responding 40 s after entry into either terminal link, synchronized with the offset of the color stimulus. The initial-link relative response rate for the right was consistently higher in comparison with a control condition in which the color stimuli occurred 20 s after entry into either terminal link. The preference for the short delay to the color conditional discriminative stimuli suggests the possibility of conditioned reinforcement by information about the relation between the line conditional discriminative stimuli and the outcomes.

Animals↗

Regeneration of the rat sciatic nerve after different conditioning lesions: effects of the conditioning interval.

Regeneration of the rat sciatic nerve was studied after a crush lesion (test lesion) on nerves previously subjected to a conditioning lesion. The test lesion was made approximately 30 mm proximal to the conditioning lesion. The period between the conditioning lesion and the test lesion was varied. Regeneration was measured by the pinch test. The conditioning procedure increased the rate of axonal elongation and decreased the initial delay. Conditioning intervals between 14 hours and 4 days were sufficient to increase the regeneration distance significantly, but only until day 4. If the conditioning interval was prolonged to 7 or 14 days, the conditioning effect persisted until day 6. A conditioning effect also was produced by transection of the sciatic nerve and by local compression produced with a silicone tube. The results of this study demonstrate that the type of injury and the conditioning intervals are important determinants in producing the conditioning effect in the rat.

Animals↗

Body condition, migration, and timing of reproduction in snow geese: a test of the condition-dependent model of optimal clutch size.

The seasonal decline of avian clutch size may result from the conflict between the advantage of early breeding (greater offspring value) and the advantage of a delay in lay date (improved body condition and hence clutch size). We tested predictions of a condition-dependent individual optimization model based on this trade-off (Rowe et al. 1994) in a long-distance migrant, the greater snow goose (Chen caerulescens atlantica), using data on condition, migration, and reproductive decisions of individuals. We closely tracked radio-marked females at their main spring staging area and on their breeding grounds. Our results were consistent with predictions of the model. Early-arriving females had a longer prelaying period and initiated their nests earlier than late arrivals. After controlling statistically for arrival date, we determined that females with high premigration condition had an earlier lay date than those in low condition. After controlling for the seasonal decline (i.e., lay date), we observed that clutch size was not related to premigration condition. Moreover, we took advantage of an unplanned manipulation of the prebreeding condition that occurred during our long-term study. We found that a reduction in condition caused a delay in lay date. However, after controlling for the seasonal decline, it did not affect clutch size. Our study indicates that geese simultaneously adjust their lay date and clutch size according to their premigration condition and migratory behavior as predicted by the condition-dependent optimization model.

Animals↗

[Equivalent cardioprotective effect of "half-conditioning" and post-conditioning in a canine model of myocardial ischemia and reperfusion].

OBJECTIVE: To study the effects of "half-conditioning", a modified postconditioning process, on myocardial injury induced by severe myocardial ischemia/reperfusion (I/R) in anesthetized dogs. METHODS: Mongrel dogs of both sexes were subjected to 40 min ischemia (coronary blood flow reduced by 80% via controlled coronary stenosis). At the end of ischemia, dogs were randomly received one of the following treatments: (1) control, reperfusion for 3 h (n = 7); (2) post-conditioning, three cycles of ischemia 30 s followed by reperfusion for 30 s and then reperfusion for 3 h (n = 7); (3) half-conditioning, coronary blood flow recovered to 50% for 2 min, then 80% for 2 min, thereafter 100% for 3 h (n = 7). Electrocardiogram (ECG), arterial blood pressure and left ventricular pressure were monitored throughout the experiment. Plasma creatine kinase (CK) and lactate dehydrogenase (LDH) activity were measured spectrophotometrically. Myocardial necrosis was defined by TTC-staining. RESULTS: Compared with control animals, arrhythmia incidence, LVEDP at 2 and 3 h reperfusion, CK and LDH were significantly reduced in animals received post-conditioning and half-conditioning treatments, infarct size as a percentage (%) of the area at risk was also significantly reduced by post-conditioning and half-conditioning treatments. No differences were observed in the post-conditioning and half-conditioning groups. CONCLUSION: Half-conditioning exerts the same cardioprotective effects on post-ischemic hearts as postconditioning.

Animals↗

The importance of cerebellar cortex and facial nucleus in acquisition and retention of eyeblink/NM conditioning: evidence for critical unilateral regulation of the conditioned response.

Experiment 1 examined acquisition of the classically conditioned eyeblink response in rabbits (Oryctolagus cuniculus) during reversible cooling lesions of the cerebellar cortex (CX), facial nucleus (FN), or lateral parvocellular reticular formation (RF). Retention was then evaluated during periods of training during reversible cooling lesions and without cooling in rabbits that had acquired the conditioned response. We found that cooling the CX did not prevent acquisition, but did retard the acquisition rate. Cooling the FN during acquisition prevented the expression of the unconditioned and conditioned response, but did not prevent the acquisition when assessed during subsequent training without cooling. Cooling the RF had no effect on the acquisition or expression of the conditioned response. During subsequent retention testing, in well-trained animals, cooling the CX did not abolish the learned response. Cooling the FN abolished both the conditioned and the unconditioned response. The results from Experiment 1 indicate that the CX is more important for acquisition than retention of the conditioned response. The FN is not important for the acquisition of the conditioned response, but is essential for the expression of the conditioned and unconditioned response. Experiment 2 examined bilateral recordings from the cerebellum in well-trained rabbits, before and during interpositus or FN cooling. We found that cooling the interpositus abolished all learning related activity in the ipsilateral or contralateral cerebellum, but did not affect the stimulus evoked responses. Cooling the FN did not abolish stimulus evoked activity or learning related activity in the cerebellum. The results emphasize the critical importance of the ipsilateral cerebellum in classical eyeblink conditioning and suggest that the memory trace for this type of learning is mediated by unilateral circuitry.

Animals↗

Effects of dexfenfluramine on glucose drinking and glucose-conditioned flavour preferences in rats: taste versus post-ingestive conditioning.

A comparison was made of the effects of dexfenfluramine (DF, 3-10 mg kg-1) on intake of and conditioning with glucose solutions varying in orostimulant properties (taste) and post-ingestive actions (calories), in rats. First, sham-feeding, using gastric-fistulated rats, was performed to assess the orostimulant properties of the solutions. Then, two experiments were done. In the first experiment, we examined the effects of DF, given at doses of 13 and 10 mg kg-1, on the intake of two glucose solutions having different orostimulant properties and different caloric values. The solutions were a mix of 1% glucose plus 0.125% saccharin (low caloric, more orostimulant), and 4% glucose (high caloric, less orostimulant). At doses of 10 mg kg-1, DF administration markedly reduced intake of both solutions (P < 0.05 vs Control Group, respectively). In second experiment, we examined the effects of DF (10 mg kg-1) on flavour preference conditioning in two parts. In the first part of the experiment, rats consumed two distinctively flavoured solutions having equal orostimulant properties but different caloric value for a conditioning period of 16 days. The solutions were a mix of 1% glucose plus 0.125% saccharin (low caloric), and 6.1% glucose (high caloric). At the end of the conditioning period, the flavour paired with ingestion of more calories was subsequently preferred (P < 0.05 vs low caloric glucose-saccharin mix). DF, when given during and after the conditioning period, attenuated this flavour-calorie conditioning (P < 0.05 vs Control Group). In the second part of the experiment, rats were conditioned with flavours associated with a mix of 20% glucose plus 0.4% citric acid and 20% glucose solutions. These solutions were equally caloric but differed in orostimulant properties. The flavour paired with better orostimulant properties was subsequently preferred (P < 0.05 vs less orostimulant glucose-citric acid mix). DF, when given during and after the conditioning period, also attenuated this flavour-flavour conditioning (P < 0.05 vs Control Group). These results suggest that DF may impair flavour preference learning.

Animals↗

A comparison of the effects of vicariously instigated classical conditioning and direct classical conditioning procedures.

Two groups of Ss received either two or 16 paired classical conditioning trails beyond the peak CR. A third group received the same stimuli as the 16 postpeak condition but in an unpaired and random order. The stimuli in all three groups were delivered directly to S. Subsequently, all three groups, including a fourth which was not given any prior direct classical conditioning, were exposed to vicariously instigated classical conditioning. This consisted of having S observe someone (model) employed by E who received the same CS as was delivered during direct conditioning. The CS was paired with the feigned arm movement of the model, simulating a reaction to shock. This vicarious classical conditioning procedure when compared to direct classical conditioning resulted in smaller GSR magnitudes for both the CRs and UCRs. Previous experience with direct classical conditional seems to have had an attenuating effect on GSR magnitude during the vicarious situation. A postexperimental questionnaire tended to support the results, and the relationship between the present study and current classical conditioning theory is discussed.

Conditioning, Classical↗

Extinction of ethanol-induced conditioned place preference and conditioned place aversion: effects of naloxone.

Four experiments examined the effect of naloxone pretreatment on the expression and extinction of ethanol-induced conditioned place preference (experiments 1, 2, 4) or conditioned place aversion (experiments 1, 3). DBA/2 J mice received four pairings of a distinctive tactile (floor) stimulus (CS) with injection of ethanol (2 g/kg) given either immediately before or after 5-min exposure to the CS. A different stimulus was paired with injection of saline. Pre-CS injection of ethanol produced conditioned place preference, whereas post-CS injection of ethanol produced conditioned place aversion. Both behaviors extinguished partially during repeated choice testing after vehicle injection. Naloxone (10 mg/kg) had little effect on the initial expression of conditioned place preference, but facilitated its extinction. Moreover, repeated naloxone testing resulted in the expression of a weak conditioned place aversion to the CS that initially elicited a place preference. In contrast, naloxone (1.5 or 10 mg/kg) enhanced expression of conditioned place aversion, thereby increasing its resistance to extinction. A control experiment (experiment 4) indicated that repeated testing with a different aversive drug, lithium chloride, did not affect rate of extinction or produce an aversion to the CS previously paired with ethanol. These findings do not support the suggestion that naloxone facilitates the general processes that underlie extinction of associative learning. Also, these data are not readily explained by the conditioning of place aversion at the time of testing. Rather, naloxone's effects appear to reflect a selective influence on maintenance of ethanol's conditioned rewarding effect, an effect that may be mediated by release of endogenous opioids. Overall, these findings encourage further consideration of the use of opiate antagonists in the treatment of alcoholism.

Alcohol Deterrents↗

Is evaluative conditioning a qualitatively distinct form of classical conditioning?

This paper contains a critical review of the claim that evaluative conditioning (EC) represents a theoretically distinct form of classical conditioning. A review of the evidence suggests that: (i) while it is claimed that EC can occur without awareness, EC studies have either adopted inappropriate statistical comparisons to demonstrate this or have failed to use the control conditions necessary to indicate that what is being measured is associative conditioning; (ii) there is no theoretical reason why conditioning without awareness might be observed in any conditioning paradigm if a relatively complex covariation assessment procedure such as that adopted in EC studies is used; and (iii) there are a variety of possible explanations for the relative resistance to extinction reported with EC, some of which allude to failure to use appropriate control conditions and others which point to specific details unique to the EC extinction procedure. Until these appropriate procedural and statistical comparisons are made, it is concluded that it is premature to assume that EC represents a form of conditioning that is theoretically distinct from other types of classical conditioning.

Animals↗

Handling blocks expression of conditioned place aversion but not conditioned place preference produced by ethanol in mice.

Previous findings implicate opioid receptors in the expression of the conditioned rewarding and aversive properties of ethanol. We have recently reported that the conditioned rewarding effect of ethanol is mediated by opioid receptors in the ventral tegmental area (VTA). We attempted to determine whether VTA opioid receptors also mediate the expression of the conditioned aversive properties of ethanol. However, the magnitude of conditioned place aversion (CPA) was not consistent with our previous findings and prevented us from making definitive conclusions. We hypothesized that the handling required to make intracranial infusions in mice alters the expression of CPA, but not conditioned place preference (CPP). Therefore, non-operated animals underwent a Pavlovian conditioning procedure for either ethanol CPA or CPP. Just before testing, half of the animals were held by the scruff of the neck to mimic intracranial infusion handling. Animals conditioned for CPA did not express CPA if they were handled. However, animals conditioned for CPP exhibited robust CPP, regardless of handling. These findings provide additional evidence that the conditioned rewarding and aversive effects of ethanol are mediated by different neural mechanisms.

Animals↗