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Background. Proximal and distal social stimulation increase ethanol drinking in humans. Purpose. Our study evaluated the effects of proximal and distal social stimulation on home-cage ethanol drink- ing in mice.Study design. Proximal cagemate drinking (PCD) proce- dures use a clear plastic barrier to separate the drinker mouse from the proximal cagemate mouse, to evaluate home-cage drinking of 10% ethanol and water. Eight groups of CD-1 mice were arranged in a 2 × 2 × 2 factorial design with two levels of sex of drinker (male vs. female), two levels of sex of cagemate (male vs. female), and two levels of distal group-housed mice in the colony room (present vs. absent). Results. Distal group-housed mice, located outside of the home cage, stimulated ethanol drinking in female drinkers and did so regardless of the sex of their proximal cagemate. This effect was observed in the male drinker but only when housed with a proximal male cagemate. Conclusion. This study provides the first report of distal social stimu- lation of ethanol drinking in mice. The distal social stimulation effect, like the effects of proximal social stimulation, was more pronounced in female drinkers.

The present experiment evaluated the effects of the Number of Cagemates (0 vs 1 vs 2) on home cage ethanol drinking during Proximal Cagemate Drinking (PCD) procedures in Male and Female CD-1 mice. Continuous-access home cage 2-bottle (ethanol vs. water) free-choice procedures were employed. PCD procedures eliminate the distracting effects of direct physical contact between Drinkers and their Cagemates on ethanol drinking by imposing a translucent plastic barrier strip between them. If direct physical contact distracts from drinking, then one Cagemate would drink more ethanol and more water than two Cagemates housed together on the same side of the barrier. This would be the case even if two Cagemates stimulated more ethanol drinking in the Drinker housed on the other side of the barrier, due to the social stimulation effects of additional Cagemates. Results revealed that the ethanol intake of Female Drinkers was directly related to the number of Cagemates on the other side of the barrier strip, but this social stimulation effect was not observed in Male Drinkers. For Male Cagemates and Female Cagemates, the single Cagemate provided elevated ethanol intake and elevated water intake relative to the ethanol intake and water intake of each Cagemate in the two Cagemates condition. The data revealed that direct physical contact between Cagemates reduced their ethanol intake, even while stimulating ethanol intake of the Drinker on the other side of the barrier, indicating that the effects of social stimulation on ethanol drinking are not entirely due to effects of modeling or peer pressure. The PCD procedures allow the evaluation of effects of a broad range of social factors on home cage ethanol drinking in mice.

The effects of social stimulation on ethanol drinking in humans may depend on the gender of the drinker, the gender of the social stimulus, and the availability of ethanol provided to the social stimulus. The present study employed the Proximal Cagemate Drinking (PCD) Procedures to evaluate the effects of the gender of the social stimulus Cagemate mouse and the effects of providing ethanol to the Cagemate mouse on the drinking of ethanol and water by the male or female CD-1 Drinker mouse. Twelve groups of subjects were arranged in a 3 × 2 × 2 factorial design with 3 levels of Cagemate Gender (Male vs. Female vs. None), 2 levels of Drinker Gender (Male vs. Female), and 2 levels of Cagemate Ethanol (Ethanol vs. No Ethanol). In the 8 groups assigned to social housing conditions, each Drinker mouse was housed with a Cagemate mouse on opposite sides of a clear plastic shoebox cage equipped with a clear plastic barrier that divided the cage lengthwise into 2 equal compartments. Six groups of Drinkers and 4 groups of Cagemates were provided with continuous access to 2 bottles (ethanol vs. water), while the 4 groups of Cagemates in the No Ethanol condition were provided with 2 bottles containing water. Results revealed that providing the Cagemate with ethanol elevated ethanol intake and ethanol preference but reduced water intake in Drinkers in Other-Gender Pairings (Male Drinker-Female Cagemate or Female Drinker-Male Cagemate) relative to Drinkers in Same-Gender Pairings (Male Drinker-Male Cagemate or Female Drinker-Female Cagemate). In contrast, when the Cagemate was not provided with access to ethanol, the opposite effects were observed. These novel PCD procedures reveal that the gender of the Cagemate and the Cagemate's access to ethanol influenced ethanol drinking in proximal-housed CD-1 Drinker mice.

Drug abuse researchers have noted striking similarities between behaviors elicited by Pavlovian sign-tracking procedures and prominent symptoms of drug abuse. In Pavlovian sign-tracking procedures, repeated paired presentations of a small object (conditioned stimulus, CS) with a reward (unconditioned stimulus, US) elicits a conditioned response (CR) that typically consists of approaching the CS, contacting the CS, and expressing consummatory responses at the CS. Sign-tracking CR performance is poorly controlled and exhibits spontaneous recovery and long-term retention, effects that resemble relapse. Sign-tracking resembles psychomotor activation, a syndrome of behavioral responses evoked by addictive drugs, and the effects of sign-tracking on corticosterone levels and activation of dopamine pathways resemble the neurobiological effects of abused drugs. Finally, the neurobiological profile of individuals susceptible to sign-tracking resembles the pathophysiological profile of vulnerability to drug abuse, and vulnerability to sign-tracking predicts vulnerability to impulsive responding and alcohol self-administration. Implications of sign-tracking for models of drug addiction are considered.

The present experiment evaluates the effects of intermittent exposure to a social stimulus on ethanol and water drinking in rats. Four groups of rats were arranged in a 2 × 2 factorial design with 2 levels of Social procedure (Intermittent Social vs Continuous Social) and 2 levels of sipper Liquid (Ethanol vs Water). Intermittent Social groups received 35 trials per session. Each trial consisted of the insertion of the sipper tube for 10 s followed by lifting of the guillotine door for 15 s. The guillotine door separated the experimental rat from the conspecific rat in the wire mesh cage during the 60 s inter-trial interval. The Continuous Social groups received similar procedures except that the guillotine door was raised during the entire duration of the session. For the Ethanol groups, the concentrations of ethanol in the sipper [3, 4, 6, 8, 10, 12, 14, and 16% (vol/vol)] increased across sessions, while the Water groups received 0% ethanol (water) in the sipper throughout the experiment. Both Social procedures induced more intake of ethanol than water. The Intermittent Social procedure induced more ethanol intake at the two highest ethanol concentration blocks (10–12% and 14–16%) than the Continuous Social procedure, but this effect was not observed with water. Effects of social stimulation on ethanol drinking are discussed.

We evaluated the effects of social interaction opportunity (SIO) and intermittent presentations of the ethanol sipper tube (IS) on autoshaping of ethanol drinking in nondeprived rats. Rats were assigned to one of seven groups. Two groups experienced brief IS, either paired with or randomly related to the response-independent raising of a guillotine door (D) revealing the presence of a conspecific male rat in a holding cage (SIO). Two control groups received similar training, respectively, except that the D revealed an empty cage, whereas a third control group received IS but neither D nor SIO. For two additional control groups, the ethanol sipper tube was continuously available during the session, with and without SIO, with both groups receiving intermittent D. In IS conditions, procedures with SIO induced more ethanol intake than did non-SIO procedures, indicating that SIO contributed to ethanol intake, but D procedures did not differ from non-D procedures, indicating that ethanol drinking was not related to the operation of the door. Groups that received training procedures providing for both SIO and IS showed more rapid initiation of ethanol intake and more rapid escalation of ethanol intake as the concentration of ethanol in the sipper tube conditioned stimulus was increased across sessions. Theoretical accounts, which are based on cue at response manipulandum/autoshaping, schedule-induced polydipsia, incentive sensitization, and intermittency-induced arousal, are considered.

Two experiments were designed to evaluate the effects of pairings of ethanol sipper conditioned stimulus (CS) with social opportunity unconditioned stimulus (US) on ethanol sipper CS-directed drinking in rats. In both experiments, rats were deprived of neither food nor water, and initiation of drinking of unsweetened 3% ethanol was evaluated, as were the effects of increasing the concentration of unsweetened ethanol (3–10%) across sessions. In Experiment 1, Group Paired ( n =8) received 35 trials per session wherein the ethanol sipper CS was presented for 10 s immediately prior to 15 s of social opportunity US. All rats initiated sipper CS-directed drinking of 3% ethanol. Increasing the concentration of ethanol in the sipper CS [(3%, 4%, 6%, 8%, 10% (vol./vol.)] across sessions induced escalation of daily g/kg ethanol intake. To evaluate the hypothesis that the drinking in Group Paired was due to autoshaping, Experiment 2 included a pseudoconditioning control that received sipper CS and social opportunity US randomly with respect to one another. All rats in Group Paired ( n =6) and in Group Random ( n =6) initiated sipper CS-directed drinking of 3% ethanol and daily mean g/kg ethanol intake in the two groups was comparable. Also comparable was daily g/kg ethanol intake, which increased for both groups with the availability of higher concentrations of ethanol in the sipper CS, up to a maximum of approximately 0.8 g/kg ethanol intake of 10% ethanol. Results indicate that random presentations of ethanol sipper CS and social opportunity US induced reliable initiation and escalation of ethanol intake, and close temporally contiguous presentations of CS and US did not induce still additional ethanol intake. This may indicate that autoshaping CR performance is not induced by these procedures, or that high levels of ethanol intake induced by factors related to pseudoconditioning produces a ceiling effect. Implications for ethanol drinking in humans are discussed.

Pavlovian autoshaping procedures provide for pairings of a small object conditioned stimulus (CS) with a rewarding substance unconditioned stimulus (US), resulting in the acquisition of complex sequences of CS-directed skeletal-motor responses or autoshaping conditioned responses (CRs). Autoshaping procedures induce higher post-session levels of corticosterone than in controls receiving CS and US randomly, and the enhanced post-session corticosterone levels have been attributed to the appetitive or arousal-inducing effects of autoshaping procedures. Enhanced corticosterone release can be induced by aversive stimulation or stressful situations, where it is often accompanied by higher levels of norepinephrine (NE) and serotonin (5-HT) in prefrontal cortex (PFC) but not in striatum (ST). Effects of autoshaping procedures on post-session corticosterone levels, NE contents in PFC, and 5-HT contents in PFC and ST were investigated in male Long-Evans rats. Post-session blood samples revealed higher corticosterone levels in the CS-US Paired group (n = 46) than in the CS-US Random control group (n = 21), and brain samples revealed higher levels of PFC NE and 5-HT in CS-US Paired group. Striatal 5-HT levels were unaltered by the autoshaping procedures. Autoshaping procedures provide for appetitive stimulation and induce an arousal-like state, as well as simultaneous stress-like changes in plasma corticosterone and monoamine levels in PFC. Autoshaping, therefore, may be useful for the study of endocrine and central processes associated with appetitive conditions.

To examine the hypothesis that Pavlovian autoshaping provides an animal learning model of drug abuse, two studies evaluated the induction of ethanol drinking by autoshaping procedures. In Experiment 1, the sipper tube conditioned stimulus (C S) contained saccharin/ethanol solution and was repeatedly paired with food as an unconditioned stimulus (US). The CS-US paired group consumed more of the 0.1% saccharin-6% ethanol solution than did the CS-US random group, revealing that autoshaping conditioned responses (CR) induce ethanol drinking not attributable to pseudo-conditioning. Experiment 2 employed saccharin-fading procedur es and showed that the paired vs random group differences in ethanol drinking were maintained, even as the saccharin was eliminate d from the solution. The results show that Pavlovian autoshaping procedures induce high volumes of ethanol drinking when the pres enta- tion of a sipper tube containing an ethanol solution precedes the response-independent delivery of food. The high volume of eth anol consumed in a brief period of time suggests that Pavlovian autoshaping may be a model of binge drinking.

The present experiment evaluated the effects of naltrexone, a non-selective opioid receptor antagonist, on post-abstinence alcohol drinking in C57BL/6NCRL and DBA/2J male mice. Home cage 2-bottle (alcohol vs. water) free-choice procedures were employed. During the pre-abstinence period, alcohol intake was much lower for the DBA/2J mice relative to the C57BL/6NCRL mice, and this strain difference was observed for groups receiving either 3% or 10% alcohol concentrations. The four-day abstinence period effectively reduced alcohol intakes (i.e., a negative alcohol deprivation effect, negative ADE) in both groups of DBA/2J mice, but had no effect on alcohol intakes in either group of C57BL/6NCRL mice. Both groups trained with 3% alcohol received the second four-day abstinence period, where the effects of acute administration of either naltrexone or saline on post-abstinence alcohol drinking were assessed. Naltrexone was more effective in reducing post-abstinence drinking of 3% alcohol in the DBA/2J mice than in the C57BL/6NCRL mice. In the DBA/2J mice, naltrexone further reduced, relative to saline-injected controls, the low levels of post-abstinence alcohol intake. Thus, the low baseline levels of alcohol drinking in DBA/2J mice were further diminished by the four-day abstinence period (negative ADE), and this suppressed post-abstinence level of alcohol drinking was still further reduced by acute administration of naltrexone. The results indicate that naltrexone is effective in reducing further the low levels of alcohol drinking induced by the negative ADE.

Animal learning studies reveal that locating the reward cue (discriminative stimulus positively correlated with the presentation of positive reinforcement) at the site of the response manipulandum (object contacted in performing the instrumental response), an arrangement referred to as CAM (cue and manipulandum), induces excessive instrumental responding. CAM induces excessive responding even when responding is negatively related to reinforcement and serves only to delay or cancel reinforcement, revealing that excessive responding induced by CAM is unrestrainable and compulsive. In addition, the response form induced by CAM resembles patterns of consummatory behaviors. Thus, animal learning studies reveal that CAM induces excessive and compulsive appetitive-consummatory responding that is triggered by objects predictive of rewarding substances. The CAM model defines conditions under which the drug-taking implement the response manipulandum at which instrumental drug-taking behavior is directed) will contribute to the development of excessive and compulsive drug-taking in humans. Implementassisted drug-taking procedures in humans provide for CAM whenever the drug-taking implement is positively correlated with the drug's reinforcing effects. This correlation is highest when the drug-taking implement is employed only to consume the drug and the drug is consumed in no other fashion. Evidence relating drug-taking implements to drug abuse is reviewed and implications for prevention and therapy are considered.

While poorly controlled alcohol drinking is a prominent symptom of alcohol abuse, its environmental determinants remain poorly understood. The Sign-Tracking Model (STM), developed by Tomie and his associates, postulates that poorly controlled alcohol drinking is due to the development of signal-directed behaviors induced by Pavlovian sign-tracking procedures. In laboratory studies of animal learning, presentation of the lever (conditioned stimulus, CS) followed by the presentation of the food (unconditioned stimulus, US) induces sign-tracking conditioned response (CR) performance, wherein rats approach and contact, then express consummatory-like responses (i.e., licking, gnawing, and chewing) directed at the lever CS. The Pavlovian sign-tracking CR is an involuntary acquired reflexive response. It is poorly controlled and elicited by the presentation of the CS. STM proposes that poorly controlled alcohol drinking in humans may be due to repeated pairings of the alcohol sipper (e.g., cocktail glass) CS with alcohol's rewarding effects US, resulting in sign-tracking CR performance. The cocktail glass CS will elicit Pavlovian sign-tracking CR performance of reflexive and involuntary alcohol intake. This paper reviews evidence in the Pavlovian conditioning literature that in animals the positive contingency between the alcohol sipper CS and alcohol US induces sign-tracking of alcohol drinking. Also reviewed is evidence that in human beings alcohol drinking is a direct function of the positive contingency between a particular alcohol glassware CS and alcohol US. Implications of these findings for the Sign-Tracking Model (STM) are discussed.

In rats, Pavlovian sign-tracking has been extensively evaluated as a model of compulsiveness in drug addiction and other addictive behaviors, but it remains unexplored in mice, a species with a wealth of genetically modified models, which makes it possible to examine gene-behavior relationships. In C57BL/6 mice, the most commonly used mouse strain for genetic studies, repeated pairings of lever conditioned stimulus (CS) with food unconditioned stimulus (US) induced Pavlovian conditioning of sign-tracking conditioned response (ST CR) performance of lever CS-directed approach, and Pavlovian conditioning of goal-tracking conditioned response (GT CR) performance of approach responses directed at the location of the food trough where the food US was delivered. The CS–US Paired group performed more ST CRs and more GT CRs during sessions 15–16 than did pseudoconditioning controls which received the lever CS and food US randomly with respect to one another. During sessions 15–16, all mice in the Paired group performed more GT CRs than ST CRs, and regression analysis revealed a positive relationship between an individual subject's tendency to perform ST CRs and GT CRs. The mice that performed more ST CRs during sessions 15–16 yielded higher plasma corticosterone levels. These data reveal stable and reliable acquisition and maintenance of ST CR performance and GT CR performance in mice; however, unlike in rats, ST CRs and GT CRs did not vary inversely within subjects. Corticosterone release, a pathophysiological marker of vulnerability to drug abuse, was positively related to ST CR performance.

Eighteen Long-Evans rats were exposed to a MULT VT 30-sec EXT schedule of water presentations. The EXT schedule was signaled by a 2500-Hz, 70-dB tone. Mean number of bites of a plastic target during atone (S−) increased across sessions, whereas the mean number of target bites during the VT component signaled byno tone (S+) decreased across sessions. Changing the multiple schedule to MULT EXT EXT produced a decrease in target bites during the tone. Reinstating the original MULT VT 30-sec EXT schedule produced an increase in number of target bites during the tone (S−). Changing the multiple schedule to VT 30-sec VT 30-sec produced a decrease in target bites during the tone. The results indicate that target biting in rats increases in the presence of the exteroceptive tone (S−) of the MULT VT 30-sec EXT schedule, and that target biting during the tone varies directly with the negative correlation between tone and water presentations.

Two experiments evaluated the effects of removing food presentations on the maintenance of drinking induced by experience with sipper — food pairings. In Exp 1, ethanol drinking was induced in non-deprived Long-Evans rats by Pavlovian conditioning procedures employing an ethanol sipper as conditioned stimulus (CS) and food pellet as unconditioned stimulus (US). The Paired/Ethanol group received presentations of the ethanol sipper CS followed immediately by the response-independent presentation of the food pellet US. The Random/Ethanol group received the ethanol sipper CS and food US randomly with respect to one another. For both groups, the concentration of ethanol in the sipper CS [(3%, 4%, 6%, 8% (vol./vol.)] was increased across sessions, and, as in previous studies employing low concentrations of ethanol in non-deprived rats (i.e., maintained with free access to food in their home cages), the two procedures induced comparable levels of sipper CS-directed ethanol drinking. Removing food US presentations had no effect on sipper CS-directed ethanol drinking in either group. In Exp 2, groups of non-deprived Long-Evans rats were trained either with water or ethanol in the sipper CS paired with food US. Removing food US presentations had no effect on ethanol drinking in the Paired/Ethanol group, but water drinking in the Paired/Water group declined systematically across sessions. Results indicate that food US presentations contribute to the maintenance of water drinking but not to the maintenance of ethanol drinking. Implications for accounts of ethanol drinking based on Pavlovian sign-tracking, behavioral economics and intermittent sipper procedures are considered.

Aims: Intermittent presentations of the ethanol sipper have been reported to induce more ethanol drinking in rats than when the ethanol sipper was continuously available during the session. This intermittent sipper effect was observed in a social drinking situation, in which subjects experienced intermittent opportunities to interact briefly with a conspecific rat. The objective of this study was to evaluate the effects of the intermittent sipper procedure in situations providing for intermittent presentations of food, and, in addition, in situations that do not provide for intermittent presentations of another rewarding event. Methods: Four groups of male Long-Evans hooded rats, arranged in a 2 × 2 factorial design with two levels of Sipper Procedure (Intermittent vs Continuous) and two levels of Food procedure (Food vs No Food), were trained in drinking chambers. During each daily session, Intermittent Sipper groups received access to the ethanol sipper during each of 25 trials of 10 s each, while Continuous Sipper groups had access to the ethanol sipper during the entire session (∼30 min). During each session, Food groups received 25 presentations of food pellets while No Food groups received no food pellets. Ethanol concentrations in the sipper [3, 4, 6, 8, and 10% (vol./vol.)] increased across sessions. Results: More rapid escalation of ethanol intake was observed in the Intermittent Sipper groups than in the Continuous Sipper groups, and this effect was observed in both the Food and No Food conditions ( P 's < 0.05), which did not differ from one another. Conclusions: Intermittent Sipper procedures provide less access to the ethanol sipper, yet induced more ethanol drinking than Continuous Sipper procedures. The intermittent sipper effect is not dependent on presentations of food. Implications for schedule-induced polydipsia and Pavlovian autoshaping are discussed. ( Received 19 August 2005; first review notified 31 October 2005; in revised form 31 December 2006; accepted 6 January 2006)

Three groups of male Long–Evans hooded rats were assessed for effects of social opportunity on drinking of ethanol or water. The ethanol/female group received intermittent presentations of a sipper containing ethanol that was followed by 15 s of social interaction opportunity with a female rat. The ethanol/male group received similar training except the social interaction opportunity was with a male rat. The water/female group received training similar to the ethanol/female group except that the sipper contained water. For the ethanol groups, the concentration of ethanol [3%, 4%, 6%, 8% and 10% (vol/vol)] in the sipper was increased across sessions. With 10% ethanol in the sipper, social opportunity with females induced more drinking and ethanol intake than did social opportunity with males. Social opportunity with females induced more intake of ethanol than water. Post-session plasma samples revealed social opportunity with females induced higher corticosterone and testosterone levels than did social opportunity with males, irrespective of the sipper fluid. This study documents, for the first time, an inter-gender effect on ethanol drinking in rats.

Previous studies of autoshaping of drinking report a positive relationship between experience with autoshaping procedures and drinking, but this effect was confounded with age, as the rats were older when they drank more. The present experiment evaluated the effects of the age of male Long-Evans hooded rats [90-days old (Younger group) vs. 135 days old (Older group)], at the beginning of the study, on drinking induced by Pavlovian autoshaping procedures. Autoshaping procedures consisted of pairings of sipper conditioned stimulus (CS) with food unconditioned stimulus (US). Rats were deprived of neither food or fluid, and sweeteners were not employed at any time during the study. For all rats (n = 32), during sessions 1-10, the sipper CS contained water. Thereafter, for rats in the Ethanol groups (n = 20), the sipper CS contained ethanol, with the concentration (1, 2, 3, 4, 5, 6%, v/v) increasing across autoshaping sessions. For rats in the Water groups (n = 12), throughout the experiment the sipper CS contained tap water (0% ethanol). Rats in the Younger group drank more ethanol and more water from the sipper CS than rats in the Older group, and across age groups there was more ethanol drinking than water drinking, an effect unlikely due to foraging for calories. Data support the hypothesis that ethanol’s pharmacological effect was to enhance autoshaping, resulting in a positive feedback loop inducing still more ethanol drinking. The younger rats were more vulnerable to autoshaping effects. Implications for models of addiction are discussed.

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Effects of autoshaping procedures (Paired versus Random) and sipper fluid [chlordiazepoxide (CDP) versus water] on sipper-directed drinking were evaluated in 32 male Long-Evans rats maintained with free access to food and water. For the Paired/CDP group (n = 16), autoshaping procedures consisted of the presentation of the CDP sipper conditioned stimulus (CS) followed by the response-independent presentation of the food unconditioned stimulus (US). The concentration of CDP in the sipper CS (0.05, 0.10, 0.15, 0.20, and 0.25 mg/ml CDP) was increased across sessions. The Paired/Water group (n = 8) received only water in the sipper CS. The Random/CDP group (n = 8) received the CDP sipper CS and food US randomly with respect to one another. The Paired/CDP group drank significantly more of the 0.20 mg/ml and 0.25 mg/ml CDP solutions than the Random/CDP control, and more fluid than the Paired/Water control group when the sipper CS for the Paired/CDP group contained the three highest concentrations of CDP. CS-Only extinction procedures reliably reduced sipper CS-directed drinking in the Paired/CDP and the Paired/Water groups, but not in the Random/CDP group. Data are consistent with the hypothesis that Pavlovian autoshaping procedures induce sipper CS-directed drinking of CDP in rats deprived of neither food nor fluid. Implications for the autoshaping model of drug abuse are discussed.

Aims: The present study evaluates the effects of pairing ethanol sipper conditioned stimulus (CS) with social opportunity unconditioned stimulus (US) on CS-directed ethanol drinking in rats. Subjects were Long-Evans male rats (n = 32) deprived of neither food nor water, and the concentration of unsweetened ethanol (3 to 16%) in the sipper CS was increased across sessions. Methods: Group Paired/Ethanol (n = 12) received the ethanol sipper CS for 10 s immediately prior to 15 s of social opportunity US. Control groups received water rather than ethanol in the sipper CS (Paired/Water), or ethanol sipper CS and US presentations randomly (Random/Ethanol), or ethanol sipper CS but no social opportunity US (Sipper Only). Results: Mean ethanol intake in the Paired/Ethanol and Random/Ethanol groups exceeded 1.0 g/kg when the sipper CS contained 12%, 14% and 16% ethanol, and higher fluid intakes were observed in the Paired/Ethanol and Random/Ethanol groups than in the Paired/Water and Sipper Only groups. Conclusions: Social opportunity increased ethanol drinking, and more so than water drinking; however, autoshaping did not induce additional ethanol drinking beyond that observed in random controls.

In two studies, we evaluated the effects of ethanol concentration and trial spacing on Pavlovian autoshaping of ethanol drinking in rats. In these studies, the brief insertion of an ethanol sipper conditioned stimulus (CS) was followed by the response-independent presentation of food unconditioned stimulus (US), inducing sipper CS-directed drinking conditioned responses (CRs) in all rats. In Experiment 1, the ethanol concentration in the sipper CS [0%-16% volume/volume (vol./vol.), in increments of 1%] was systematically increased within subjects across autoshaping sessions. Groups of rats received sipper CS-food US pairings (Paired/Ethanol), a CS-US random procedure (Random/Ethanol), or water sipper CS paired with food US (Paired/Water). In Experiment 2, saccharin-fading procedures were used to initiate, in the Ethanol group, drinking of 6% (vol./vol.) ethanol in 0.1% saccharin or, in the Water group, drinking of tap water in 0.1% saccharin. After elimination of saccharin, and across days, the duration of access to the sipper CS during each autoshaping trial was increased (5, 10, 12.5, 15, 17.5, and 20 s), and subsequently, across days, the duration of the mean intertrial interval (ITI) was increased (60, 90, 120, and 150 s). In Experiment 1, Paired/Ethanol and Random/Ethanol groups showed higher intake of ethanol, in terms of grams per kilogram of body weight, at higher ethanol concentrations, with more ethanol intake recorded in the Paired/Ethanol group. In Experiment 2, the Ethanol group drank more than was consumed by the Water group, and, for both groups, fluid intake increased with longer ITIs. Results support the suggestion that autoshaping contributes to sipper CS-directed ethanol drinking.

The effects of autoshaping procedures (paired vs. random) and sipper fluid (ethanol vs. water) on sipper-directed drinking were evaluated in male Long-Evans rats maintained with free access to food and water. For the paired/ethanol group (n=16), autoshaping procedures consisted of presenting the ethanol sipper (containing 0% to 28% unsweetened ethanol) conditioned stimulus (CS) followed by the response-independent presentation of food unconditioned stimulus (US). The random/ethanol group (n=8) received the sipper CS and food US randomly with respect to one another. The paired/water group (n=8) received only water in the sipper CS. The paired/ethanol group showed higher grams per kilogram ethanol intake than the random/ethanol group did at ethanol concentrations of 8% to 28%. The paired/ethanol group showed higher sipper CS-directed milliliter fluid consumption than the paired/water group did at ethanol concentrations of 1% to 6%, and 15%, 16%, 18%, and 20%. Following a 42-day retention interval, the paired/ethanol group showed superior retention of CS-directed drinking of 18% ethanol, relative to the random/ethanol group, and superior retention of CS-directed milliliter fluid drinking relative to the paired/water group. When tested for home cage ethanol preference using limited access two-bottle (28% ethanol vs. water) procedures, the paired/ethanol and random/ethanol groups did not differ on any drinking measures.

Effects of experience with Pavlovian autoshaping procedures on lever-press autoshaping conditioned response (CR) performance and 3H-8-OH-DPAT-labeled binding of 5-HT1a receptors as well as 125I-LSD-labeled binding of 5-HT2a receptors were evaluated in four groups of male Long-Evans hooded rats. Two groups of rats (Group Paired High CR and Group Paired Low CR) received Pavlovian autoshaping procedures wherein the presentation of a lever (conditioned stimulus, CS) was followed by the response-independent presentation of food (unconditioned stimulus, US). Rats in Group Paired High CR (n=12) showed more rapid CR acquisition and higher asymptotic levels of lever-press autoshaping CR performance relative to rats in Group Low CR (n=12). Group Omission (n=9) received autoshaping with an omission contingency, such that performing the lever-press autoshaping CR resulted in the cancellation the food US, while Group Random (n=9) received presentations of lever CS and food US randomly with respect to one another. Though Groups Omission and Random did not differ in lever-press autoshaping CR performance, Group Omission showed significantly lower levels of 3H-8-OH-DPAT-labeled 5-HT1a binding in post-synaptic areas (frontal cortex, septum, caudate putamen), as well as significantly higher plasma corticosterone levels than Group Random. In addition, Group Random showed higher levels of 3H-8-OH-DPAT-labeled 5-HT1a binding in pre-synaptic somatodendritic autoreceptors on dorsal raphe nucleus relative to each of the other three groups. Autoradiographic analysis of 125I-LSD-labeled 5-HT2a receptor binding revealed no significant differences between Groups Paired High CR and Paired Low CR or between Groups Omission and Random in any brain regions.

Aims: This study asks if repeated Pavlovian pairings of a sipper tube (conditioned stimulus, CS) with food (unconditioned stimulus, US) will induce Pavlovian autoshaping conditioned responses (CRs), consisting of drinking of either 6% ethanol or wat er from the sipper CS. This study also tests predictions derived from the autoshaping model by asking if sipper CS-directed drinking wi ll be retained, despite the absence of training for several weeks, and, in addition, if drinking rate is a negative function of sippe r CS duration. Methods: Autoshaping procedures, conducted in two daily sessions, consisted of the brief insertion of the sipper tube CS followed by the response-independent presentation of food US. For the Ethanol group ( n = 8), the sipper CS contained 6% ethanol, whereas for the Water group (n = 8), the sipper CS contained tap water. Saccharin fading procedures were employed, whereas for both groups, during days 1-19, the sipper CS contained 0.1% saccharin, and thereafter across training days the concentration of saccharin was gradu ally reduced (0.07, 0.035, 0.0%). Following elimination of saccharin, both groups were maintained in their home cages during a 27-da y retention interval, and then re-evaluated for autoshaping of drinking of unsweetened ethanol and water. Thereafter, across days , the duration of access to the sipper CS (5.0, 7.5, 10.0, 15.0 s) during each autoshaping trial was increased. Results: Both groups increased drinking across the first 19 days of training with sipper CS-food US pairings, and, at 0.0% saccharin, the Ethanol group consumed 14.76 ml of 6% ethanol per day, resulting in a daily ethanol consumption of 2.77 g/kg. For both groups, daily levels of drinkin g before and after the 27-day retention interval were comparable, attesting to the durability of the acquired drinking effects. At each CS duration, the Ethanol group consumed more millilitres of fluid per day than did the Water group, and for the Ethanol group, peak drinking of 24.0 ml of 6% ethanol per day was observed at the 10 s CS duration. For both groups, drinking rate (millilitres of fluid consum ed per second of CS duration), was a declining monotonic function of CS duration, resulting in a daily ethanol consumption of ~4.2 g/k g for the Ethanol group. Conclusions: These data reveal that these sipper CS-food US autoshaping procedures induce drinking in rats that is durable and negatively related to increasing CS duration. The effects of both variables are consistent with the hypothesis t hat drinking from the sipper CS is a Pavlovian autoshaping CR. Autoshaping of drinking in the Water group is observed despite the absence of water deprivation, and even more fluid is consumed by the Ethanol group than by the Water group. The high volumes of ethanol consumed during brief daily sessions suggest that Pavlovian autoshaping procedures may provide an animal learning model of binge drinkin g.

Pavlovian autoshaping conditioned responses (CRs) are complex sequences of conditioned stimulus (CS)-directed skeletal-motor responses that are elicited by CS objects predictive of food unconditioned stimulus (US). Autoshaping CRs are observed under conditions known to be conducive to elevations in plasma corticosterone levels, as, for example, in response to the eating of food as well as in response to signals predictive of food. Two experiments investigated the relationships between Pavlovian autoshaping procedures, the performance of Pavlovian autoshaping CRs, and plasma corticosterone levels in male Long–Evans rats. In Experiment 1, rats in the CS–US paired group (n=30) were given 20 daily sessions of Pavlovian autoshaping training wherein the insertion of a retractable lever CS was followed by the response-independent presentation of the food US. Tail blood samples obtained after the 20th autoshaping session revealed higher plasma corticosterone levels in the CS–US paired group than in the CS–US random control group (n=10). In Experiment 2, rats (n=35) were assessed for basal plasma corticosterone levels 2 weeks prior to autoshaping training. Plasma samples obtained immediately following the first autoshaping session, and prior to the acquisition of lever-press autoshaping CR performance, revealed higher plasma corticosterone levels in the CS–US paired group (n=24) relative to basal levels. This effect was not observed in the CS–US random control group (n=11). Data suggest that corticosterone release is a physiological endocrine Pavlovian CR induced by lever CS–food US pairings during Pavlovian autoshaping procedures, rather than a by-product of autoshaping CR performance. Implications of the link between autoshaping procedures and corticosterone release are discussed.

Autoshaping conditioned responses (CRs) are reflexive and targeted motor responses expressed as a result of experience with reward. To evaluate the hypothesis that autoshaping may be a form of impulsive responding, within-subjects correlations between performance on autoshaping and impulsivity tasks were assessed in 15 Long-Evans hooded rats. Autoshaping procedures [insertion of retractable lever conditioned stimulus (CS) followed by the response-independent delivery of food (US)] were followed by testing for impulsive-like responding in a two-choice lever-press operant delay-of-reward procedure (immediate small food reward versus delayed large food reward). Delay-of-reward functions revealed two distinct subject populations. Subjects in the Sensitive group (n=7) were more impulsive-like, increasing immediate reward choices at longer delays for large reward, while those in the Insensitive group (n=8) responded predominantly on only one lever. During the prior autoshaping phase, the Sensitive group had performed more autoshaping CRs, and correlations revealed that impulsive subjects acquired the autoshaping CR in fewer trials. In the Sensitive group, acute injections of ethanol (0, 0.25, 0.50, 1.00, 1.50 g/kg) given immediately before delay-of-reward sessions yielded an inverted U-shaped dose-response curve with increased impulsivity induced by the 0.25, 0.50, and 1.00 g/kg doses of ethanol, while choice strategy of the Insensitive group was not influenced by ethanol dose. Ethanol induced impulsive-like responding only in rats that were flexible in their response strategy (Sensitive group), and this group also performed more autoshaping CRs. Data support the hypothesis that autoshaping and impulsivity are linked.

Approach responses, consummatory behaviors, and directed motor responses maintained by food reward resemble autoshaping CRs and are increased by lower doses of ethanol. This study evaluated the effects of presession i.p. injections of ethanol doses (0.00, 0.25, 0.50, 0.70. or 1.00 g/kg) on the acquisition of lever-press autoshaping CR performance in groups of male Long-Evans hooded rats. Paired groups received 15 daily sessions of Pavlovian autoshaping procedures, wherein the insertion of a retractable lever for 5 s (CS) was followed by the response-independent presentation of food (US). Ethanol facilitated lever-press autoshaping CR acquisition, as revealed by dose-related increases in the number of trials on which CRs were performed. The form of the dose-effect curve was inverted U-shaped with maximal responding induced during sessions 1-5 by the 0.70 g/kg ethanol dose. A similar dose-effect curve was observed during sessions 11-15, revealing that the effects of ethanol on autoshaping CR performance were relatively stable. A pseudoconditioning control group injected presession with 0.50 g/kg ethanol received training wherein the food US was presented randomly with respect to the lever CS. Few lever-presses were performed by the Random 0.50 group, indicating that ethanol's effects on autoshaping CR acquisition and maintenance observed in the Paired 0.50 group were not due to its psychomotor activating effects. A non-injection control group performed more autoshaping CRs than did the control group injected presession with saline, indicating that daily presession i.p. injections per se suppress autoshaping CR performance. Results reveal that low doses of ethanol enhance Pavlovian conditioning of directed motor and consummatory-like responding maintained by food reward. Implications for autoshaping accounts of impulsivity and drug abuse are considered.

1. 1. Pigeons were trained to discriminate chlordiazepoxide (CDP) from saline using two-key food reinforced drug discrimination procedures. Discriminative control by CDP was maintained despite extended training with vehicle-like doses of CDP, by using a modified “fading” procedure that provided for a mixture of drug discrimination training sessions preceded by an i.m. injection of either 8.0 mg/kg CDP, or a lower training dose of CDP (4.0, 2.8, 2. 0, 1.4, 1.0, 0.7, or 0.5 mg/kg CDP), or saline. The lower training dose was decreased across blocks of sessions. 2. 2. Four lower training doses (1.4, 1.0, 0.7, and 0.5 mg/kg CDP) were retrained, with 10 min of 98 dB of noise administered 75 min prior to each drug discrimination training session. Presession exposure to noise increased percent CDP-appropriate choices for each of the four lower training doses by 15–20% over those obtained previously. 3. 3. It is concluded that brief presession exposure to loud noise increases sensitivity to the discriminative stimulus effects of low training doses of CDP.

Female Long-Evans rats were trained to discriminate d-amphetamine (0.8 mg/kg) vs. saline in a food-reinforced two-lever operant task. Fifteen rats (fast group) acquired the discrimination rapidly, achieving criterion (eight correct choices within ten sessions) during the first 10 sessions (mean sessions to criterion = 10.0). The remaining eight rats (slow group) made at least three errors during the first 10 sessions and required additional drug discrimination training to achieve criterion (mean sessions to criterion = 15.9). When a rat had completed a minimum of 30 two-lever discrimination training sessions and, in addition, provided 10 correct choices within 10 sessions, generalization testing with lower doses of d-amphetamine was initiated. The fast group made more d-amphetamine-appropriate choices during the generalization test and generalized more to the 0.2 mg/kg d-amphetamine test dose than did the slow group, though the number of training sessions prior to generalization testing was comparable across groups. Results suggest that when the training drug is easily discriminated, fast learners generalize more, even when groups receive comparable amounts of training prior to generalization testing, and this effect is observed in female rats.

Appetitive instrumental discrimination learning procedures provide for CAM (cue and manipulandum) when the reward cue (discriminative stimulus positively correlated with positive reinforcement) is located at the response manipulandum (object that when contacted or manipulated defines the performance of the instrumental response). Evidence reviewed shows that CAM induces excessive and compulsive instrumental responding relative to otherwise comparable non-CAM control procedures. In humans, symptoms of drug abuse are particularly likely when the drug-taking implement (response manipulandum at which instrumental drug-taking is directed) is also predictive of the drug's rewarding effects (reward cue). Evidence that the predictive relationship between a drug-taking implement and drug reward relates to drug abuse is reviewed, and implications for treatment and prevention are considered. CAM is related to neurobiological models of drug abuse that emphasize the role of the neurotransmitter dopamine (DA). CAM produces convergence of DA-mediated responding for conditioned reinforcement with DA mediation of psychomotor activation and incentive-motivational processes to yield reflexive cue-directed responding not observed in non-CAM controls.

Procedures are reported that maintain control by the drug cue during and after drug discrimination training with lower doses that yield predominantly vehicle-appropriate choices. Twelve pigeons were trained to discriminate chlordiazepoxide (CDP) from saline using two-key (drug vs. vehicle) drug discrimination procedures. Intermixed within each block of 30 sessions were nine sessions of training with 8.0 mg/kg CDP, nine with one of seven lower training doses (4.0, 2.8, 2.0, 1.4, 1.0, 0.7, or 0.5 mg/ kg CDP), and 12 with saline. The lower training dose was decreased across blocks. The three lowest training doses (1.0, 0.7, and 0.5 mg/kg CDP) yielded predominantly saline-appropriate choices but had no effect on discrimination of 8.0 mg/kg CDP or saline. Three doses (2.0, 1.4, and 1.0 mg/kg CDP) were retrained, and each yielded percentages of drug-appropriate choices nearly identical to those obtained during previous training. This drug discrimination procedure maintains control by the drug cue during and after training with vehicle-like doses of the training drug and may allow for repeated assessment of effects of low training doses.

The present experiment explores the effects of the response (1-sec occupancy of a target area in an open field)-reinforcer (intracranial stimulation) contingency on time allocation in the open field in rats. The probability of reinforcement given response ( X ) and the probability of reinforcement given nonresponse ( Y ) were varied randomly across sessions within a subject. The 21 contingency treatments explored included all possible combinations of values (0, .1, .2, .3, .4, .5) of X and Y such that X ≥ Y . The results indicate that rate of acquisition and asymptotic level of time allocation preference to the target area are negatively related to the value of Y (for any given value of X ). Variations in X (for any given value of Y ) were less effective. Evaluation of proposed contingency metrics revealed that the Weber fraction (X − Y) X most closely approximates performance, and that the value of the difference detection threshold derived from the Weber fraction is a constant.

Four experiments explored various applications of the retardation test of inhibition following discriminative autoshaping. In all studies, discriminative autoshaping consisted of food-reinforced presentations of a green key-light CS+ and nonreinforced presentations of a vertical white line on a green background CS−. In Experiment 1, the inhibitory properties of the vertical Une CS− were assessed by comparing the acquisition of keypecking to the now-reinforced vertical line CS in groups previously receiving discriminative autoshaping (as above), discriminative autoshaping with a red key CS−, and nondiscriminative autoshaping. The results indicated that the former CS− was retarded in being transformed into a CS+. In Experiment 2, the discriminative autoshaping procedure was followed by testing for acquisition with independent groups receiving one of four different CSs differentiated by line orientation. The results indicated that the orientation attribute of the CS− was inhibitory, in that a between-subjects resistance-to-reinforcement gradient of inhibition was obtained. In Experiment 3, discriminative autoshaping was followed by a within-subjects resistance-to-reinforcement generalization test based on line orientation, which failed to yield an orderly gradient. The implementation of a DRO contingency in the within-subjects test (Experiment 4) was ineffective in generating an incremental gradient. Implications for inhibitory assessment methodology are discussed.

Phencyclidine (PCP), naloxone and haloperidol were administered alone and in combination to rats trained to drink sweetened-condensed milk during a 20 min daily session. PCP (1.0–16.0 mg/kg) produced a dose-dependent decrease in milk intake. All doses of naloxone (0.1–16.0 mg/kg) produced approximately a 30% decrease in milk intake. Haloperidol (0.125 mg/kg) had virtually no effect on milk intake. When a dose of naloxone which reduced milk intake by approximately 30% (8.0 mg/kg) was administered as a pretreatment to the PCP, the PCP curve was shifted to the left (lowered) to that degree. When haloperidol (0.125 mg/kg) was administered as a pretreatment to the PCP, the PCP dose-response curve was shifted 1.5 fold to the right. These interactions are similar to those observed in other behavioral paradigms and are discussed in reference to PCP's actions as an indirect dopaminergic agonist.

The present experiment explores the effects of the response (1-sec occupancy of a target area in an open field)—reinforcer (intracranial stimulation) contingency on time allocation in the open field in rats. The probability of reinforcement given a response (X) and the probability of reinforcement given the absence of a response (Y) were varied randomly across sessions within a subject. The following (X, Y) values were utilized: (.05, 0), (.15, 0), (.25, 0), (.15, .05), and (.15, .15). The results of this experiment indicate that rate of acquisition of time allocation preference is uniformly rapid during all contingency treatments wherein Y = 0 and is negatively related to the value of Y when X = .15. The relationship between the asymptote of the time allocation acquisition function and the value of X (when Y = 0) is positively sloped and negatively accelerated, while the relationship between asymptote and the value of Y (when X = .15) is negatively sloped with zero acceleration. Proposed contingency metrics are evaluated.

In Experiment 1, pigeons exposed to US ONLY pretraining were observed to be retarded in the acquisition of autoshaping relative to naive controls; however, gross changes in contextual stimuli between pretraining and testing alleviated the retardation effect. In Experiment 2, groups of pigeons exposed to CS ONLY, US ONLY, or random CS-US presentations (TRC) were tested for the acquisition of autoshaping. The US ONLY and TRC groups were retarded relative to naive controls. The context change manipulation eliminated the US ONLY retardation effect and attenuated, but did not eliminate, the TRC retardation effect. Context blocking accounts for the US ONLY effect and contributes to the TRC effect; however, context-independent retardation following TRC pretraining suggests the operation of the learned irrelevance cognition.

Compared with their performance with localized (on-key) visual stimuli, pigeons are notoriously poor at performing go/no-go discriminations when keypecking for food in the presence of auditory discriminative stimuli. The difference might reflect the fact that an aversive visual onkey stimulus signaling nonreward can be escaped by looking away and not pecking, which contributes to the measure of good discriminative performance, while an auditory stimulus cannot be escaped. In Experiment 1, discriminative performance was significantly improved by providing pigeons with a response incompatible with keypecking by which they could escape a tone S+ and a tone S−. However, the pattern, frequency, and duration of escape responses were found to be insufficient to explain the improvement. In Experiment 2, it was found that the capacity to escape only S+ or only S− enhanced discriminative performance as much as the capacity to escape both. It is theorized that the Pavlovian relationship between the absence of the discriminative stimuli and the nonoccurrence of food might transfer to the instrumental relationships learned in a go/no-go discrimination. The possibility that intermittent stimuli command more attention than continuous stimuli is also considered.

Four groups of pigeons were tested for the acquisition of autoshaping to a green key CS following 30 days of pretraining involving intermittent, unsignaled US (food) presentations. The groups were arranged in a 2 by 2 factorial design with two levels of pretraining schedule (VT 30 sec vs. VT 90 sec) and two levels of test schedule (VT 30 sec vs. VT 90 sec). The data revealed a main effect of test schedule such that subjects tested under the VT 90-sec schedule acquired the keypeck CR faster than subjects tested under the VT 30-sec schedule. There was no main effect of pretraining schedule and no interaction effect between pretraining and testing schedules. Implications for theories of acquisition and retardation of autoshaping are discussed.

In Experiment 1, three groups of pigeons were autoshaped and then administered one of three different response-elimination procedures. Group TRC (truly random control) and Group Backward (backward conditioning) ceased responding more rapidly than Group CS-only. In a subsequent reacquisition test with a novel CS, Groups TRC and Backward were retarded relative to Group CS-only. In Experiment 2, the CS-only and TRC response-elimination treatments were not differentially effective in extinguishing the response. The treatments were followed either by five sessions of unpredictable US presentations (US-only) or by five sessions of remaining in their home cages (hold) prior to the reacquisition test. The TRC treatment retarded reacquisition relative to the CS-only treatment; the US-only posttreatment manipulation failed to reliably retard reacquisition relative to Hold, although retarding effects of US-only are discernible in a block-by-block analysis. Applications and limitations of a context-blocking account of these results are discussed.

In three experiments, groups of pigeons were tested for wavelength generalization of auto-shaped key-pecking following different types of training. In Experiment I, one group received auto-shape trials with a 555-nm CS. Another group received auto-shape trials with a 555-nm CS and a white CS. A third group received auto-shape trials with a 555-nm CS and a white CS, except the white CS was nonreinforced. The third group yielded the sharpest gradient, whereas the second group yielded the flattest gradient. In Experiment II, one group received auto-shape trials with a 555-nm CS. A second group received auto-shape trials with a 555-nm CS and a compound CS consisting of a vertical white line on a 555-nm background. A third group received auto-shape trials with a 555-nm CS and a compound CS, except that the compound was nonreinforced. The third group yielded the sharpest wavelength gradient, whereas the second group yielded the flattest. In Experiment III, exposure differences to 555 nm in Experiment II resulting from differential speeds of auto-shape acquisition were controlled by the use of an ITI manipulation. Amount of exposure to 555 nm was shown not to be responsible for the results of Experiment II.

In Experiment 1, two groups of pigeons were autoshaped to a green keylight CS and then administered either CS only or truly random control (TRC) response-elimination procedures with the green keylight CS. The groups ceased responding at comparable rates. In a subsequent reacquisition test with a vertical-line key stimulus, the group administered CS only during response elimination reacquired the keypecking CR more rapidly. The two groups were then administered the alternative response-elimination treatment with the vertical-line CS. Again, the groups ceased responding at comparable rates. In a subsequent reacquisition test with a red keylight CS, the group administered CS only during the immediately preceding response-elimination phase reacquired the keypecking CR more rapidly. In Experiment 2, following initial acquisition, the CS-only and TRC response-elimination treatments were administered under the context-change and no-context change conditions. The TRC/context-change and CS-only/context-change groups ceased responding more rapidly than either the TRC/ no-context-change or CS-only/no-context-change groups. In subsequent reacquisition to a novel CS, the CS-only/no-context-change group reacquired the fastest, the TRC/no-context-change group reacquired the slowest, and the CS-only/context-change and TRC/context-change groups reacquired at similar intermediate rates. Implications of these results for the context-blocking hypothesis are discussed.