Repeated Δ-9-Tetrahydrocannabinol administration dose dependently increases stablished schedule-induced drinking.

RATIONALE: Schedule-induced drinking (SID) reproduces an excessive and repetitive behavioural pattern that has led to propose this procedure as an animal model to study compulsive behaviours. Although it is known that cannabis can cause several adverse effects, in recent years there has been great interest in the medical application of cannabis derivatives for obsessive-compulsive related disorders. OBJECTIVES: The present study investigated the effects of repeated THC administration on rates of previously acquired SID, as well as the possible alteration of its temporal distribution along inter-food intervals. METHODS: Male Wistar rats acquired SID under a 30 min fixed-time 30-sec food delivery schedule (from 30 to 43 sessions to reach a stable level). Thereafter, 5 or 10 mg/kg daily i.p. injections of THC or vehicle were repeatedly administered for 7 days to evaluate the effects on SID. RESULTS: Repeated THC administration at a dose of 5 mg/kg resulted in an increase on licking. Surprisingly, no effects on SID were observed with the 10 mg/kg dose. However, magazine entries were reduced with both THC doses. THC also modified the temporal distributions of licking and magazine entries during inter-food intervals. CONCLUSIONS: The present results show that repeated THC administration may (i) increase induced licking at moderate doses, (ii) reduce magazine entries, and (iii) affect the temporal pattern of SID. These findings suggest that THC does not appear to be beneficial to reduce compulsive behaviour in this animal model, while another collateral effect of THC -such as a greater habitual-like behaviour- needs to be considered.

Environmental enrichment accelerates the acquisition of schedule-induced drinking in rats.

Environmental enrichment (EE) provides an improvement in the housing conditions of experimental animals, such as laboratory rats, with greater physical and social stimulation through toys and company in the home cages. Its use is known to influence performance of experimental protocols, but these effects have not been well determined in the schedule-induced drinking (SID) procedure. The main goal of this study was to investigate the effects of EE on the acquisition of SID in 24 12-week-old male Wistar rats, divided into two groups, a group with EE housed with toys and companions, and a group without enrichment in individual housing conditions without toys (social isolation and no environmental enrichment, INEE). A total of 25 sessions, under a fixed time 30 s food reinforcement schedule and with access to water in the experimental chambers were carried out. Sessions lasted 30 min. The results showed that the EE group developed faster the excessive drinking pattern of SID, and drank to higher levels, than the INEE group. The greater development of SID in the EE group contradicts the view of schedule-induced behavior as linked to stress reduction and better suits with the conception of induction related to positive reinforcement.

Schedule-induced alcohol intake during adolescence sex dependently impairs hippocampal synaptic plasticity and spatial memory.

In a previous study, we demonstrated that intermittent ethanol administration in male adolescent animals impaired hippocampus-dependent spatial memory, particularly under conditions of excessive ethanol administration. In this current study, we subjected adolescent male and female Wistar rats an alcohol schedule-induced drinking (SID) procedure to obtain an elevated rate of alcohol self-administration and assessed their hippocampus-dependent spatial memory. We also studied hippocampal synaptic transmission and plasticity, as well as the expression levels of several genes involved in these mechanisms. Both male and female rats exhibited similar drinking patterns throughout the sessions of the SID protocol reaching similar blood alcohol levels in all the groups. However, only male rats that consumed alcohol showed spatial memory deficits which correlated with inhibition of hippocampal synaptic plasticity as long-term potentiation. In contrast, alcohol did not modify hippocampal gene expression of AMPA and NMDA glutamate receptor subunits, although there are differences in the expression levels of several genes relevant to synaptic plasticity mechanisms underlying learning and memory processes, related to alcohol consumption as Ephb2, sex differences as Pi3k or the interaction of both factors such as Pten. In conclusion, elevated alcohol intake during adolescence seems to have a negative impact on spatial memory and hippocampal synaptic plasticity in a sex dependent manner, even both sexes exhibit similar blood alcohol concentrations and drinking patterns.

Physical activity reduces alcohol consumption induced by reward downshift.

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. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Chronic ∆-9-tetrahydrocannabinol administration delays acquisition of schedule-induced drinking in rats and retains long-lasting effects.

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.

Effects of partial reinforcement on autoshaping in inbred Roman high- and low-avoidance rats.

Individuals trained under partial reinforcement (PR) typically show a greater resistance to extinction than individuals exposed to continuous reinforcement (CR). This phenomenon is referred to as the PR extinction effect (PREE) and is interpreted as a consequence of uncertainty-induced frustration counterconditioning. In this study, we assessed the effects of PR and CR in acquisition and extinction in two strains of rats, the inbred Roman high- and low-avoidance (RHA and RLA, respectively) rats. These two strains mainly differ in the expression of anxiety, the RLA rats showing more anxiety-related behaviors (hence, more sensitive to frustration) than the RHA rats. At a neurobiological level, mild stress is known to elevate corticosterone in RLA rats and dopamine in RHA rats. We tested four groups of rats (RHA/CR, RHA/PR, RLA/CR, and RLA/PR) in two successive acquisition-extinction phases to try to consolidate the behavioral effects. Animals received training in a Pavlovian autoshaping procedure with retractable levers as the conditioned stimulus, food pellets as the unconditioned stimulus, and lever presses as the conditioned response. In Phase 1, we observed a PREE in lever pressing in both strains, but this effect was larger and longer lasting in RHA/PR than in RLA/PR rats. In Phase 2, reacquisition was fast and the PREE persisted in both strains, although the two PR groups no longer differed in lever pressing. The results are discussed in terms of frustration theory and of uncertainty-induced sensitization of dopaminergic neurons.