Rationale Schedule-induced drinking (SID) is a behavioural phenomenon characterized by an excessive and repetitive drinking pattern with a distinctive temporal distribution that has been proposed as a robust and replicable animal model of compulsivity. Despite cannabis currently being the most widely consumed illicit drug, with growing interest in its clinical applications, little is known about the effects of ∆-9-tetrahydrocannabinol (THC) on SID. Objectives The effects of chronic and acute THC administration on SID acquisition, maintenance and extinction were studied, as were the effects of such administrations on the distinctive temporal distribution pattern of SID. Methods THC (5 mg/kg i.p.), or the corresponding vehicle, was administered to adult Wistar rats for 14 days in a row. Subsequently, THC effects on SID acquisition were tested during 21 sessions using a 1-h fixed-time 60-s food delivery schedule. Acute effects of THC were also evaluated after SID development. Finally, two extinction sessions were conducted to assess behavioural persistence. Results The results showed that previous chronic THC treatment delayed SID acquisition and altered the distinctive behavioural temporal distribution pattern during sessions. Moreover, acute THC administration after SID development decreased SID performance in animals chronically pre-treated with the drug. No great persistence effects were observed during extinction in animals pre-treated with THC. Conclusions These results suggest that chronic THC affects SID development, confirming that it can disrupt learning, possibly causing alterations in time estimation, and also leads to animals being sensitized when they are re-exposed to the drug after long periods without drug exposure.

Schedule induction refers to the process of behavior being developed during inter-reinforcement intervals without explicit arranged contingency between its occurrence and the delivery of reinforcement but only by the repeated occurrence of intermittent scheduled reinforcers.

In Pavlovian autoshaping, sign-tracking responses (lever pressing) to a conditioned stimulus (CS) are usually invigorated under partial reinforcement (PR) compared to continuous reinforcement (CR). This effect, called the PR acquisition effect (PRAE), can be interpreted in terms of increased incentive hope or frustration-induced drive derived from PR training. Incentive hope and frustration have been related to dopaminergic and GABAergic activity, respectively. We examined the within-trial dynamics of sign and goal tracking in rats exposed to 20-s-long lever presentations during autoshaping acquisition under PR vs. CR conditions under the effects of drugs tapping on dopamine and GABA activity. There was no evidence of the PRAE in these results, both groups showing high, stable sign-tracking response rates. However, the pharmacological treatments affected behavior as revealed in within-trial changes. The dopamine D2 receptor agonist pramipexole (0.4 mg/kg) suppressed lever pressing and magazine entries relative to saline controls in a within-subject design, but only in PR animals. The allosteric benzodiazepine chlordiazepoxide (5 mg/kg) failed to affect either sign or goal tracking in either CR or PR animals. These results emphasize the roles of dopamine and GABA receptors in autoshaping performance, but remain inconclusive with respect to incentive hope and frustration theories. Some aspects of within-trial changes in sign and goal tracking are consistent with a mixture of reward timing and response competition.

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Increased voluntary consumption of alcohol and other anxiolytics has been demonstrated in animals after experiencing frustrative reward devaluation (downshift) or omission. These results have been interpreted in terms of emotional self-medication. In the present study, we analyzed whether voluntary physical activity reduces alcohol intake induced by reward downshift. Sixty-four male Wistar rats were divided into eight groups (n = 8). Thirty-two (downshifted) animals received 32% sucrose during 10 preshift sessions (5 min), followed by 4% sucrose during five postshift sessions, whereas 32 (unshifted) controls were always exposed to 4% sucrose. Immediately after each consummatory session, animals were exposed to a 2-hr two-bottle preference test involving 32% alcohol versus water or water versus water. Half of the animals had also access to a wheel for voluntary running during the preference test. The results showed lower sucrose consumption in downshifted groups compared with unshifted controls (the frustrative reward downshift effect). Reward downshift significantly increased alcohol intake, this effect being absent in downshifted animals with access to the wheel. These findings suggest that physical exercise could be useful to prevent alcohol self-medication induced by frustrative nonreward.