Short-term contextual sensitisation and conditioned hyperkinesia produced by cocaine in suckling rats aged 4–10 days and 14–20 days

Abstract.

Rationale: It was hypothesised that the failure to generate sensitisation to the behavioural effects of a motor stimulant in suckling rats was mainly due to not pairing the drug with the test context during chronic pretreatment. Objective: This study probed the capabilities of neonatal and infant rat pups to show short-term context-specific sensitisation and conditioned drug activity produced by cocaine. Methods: Two similar experiments were conducted on rat pups aged 4–10 days or 14–20 days, each experiment comprising three phases: a sensitisation phase (days 4–8 and days 14–18 of age), a test session under cocaine for context specificity of sensitisation (day 9 and day 19 of age) and a test session under saline for conditioned drug effects (day 10 and day 20 of age). Over five daily sessions, pups first received an injection of either 16 mg/kg cocaine (paired group) or saline (unpaired group) in test chambers, and 110 min later the converse injections in the vivarium (in a cage that was different from the home cage). A third group received saline in both contexts. Behaviour was scored using videotapes. Results: Sensitisation developed in the paired groups at both ages. In 4- to 10-day-old pups, sensitisation was expressed via locomotion (matrix crosses) and also horizontal and vertical activities (categories comprising several age-specific movements). In 14- to 18-day-old pups, it was displayed by increases in head movements and vertical activity, and by a decline in stationary position. These effects were confirmed to be context specific on the test sessions (day 9 or day 19), the paired groups producing by far the greatest values. On the conditioning test, the paired groups also produced the greatest amounts of the above-mentioned behaviours, revealing a conditioned drug effect. Additionally, the conditioned effect scores were higher than those of two additional groups that had been treated similarly to the others but outside the chamber until the two tests (controlling for a withdrawal effect and possible novelty-induced activity in the test context). There were no differences between these unexposed groups, indicating that no abstinence effect occurred. Conclusions: The results demonstrate that neonatal rats are capable of showing physiological/non-contextual cocaine-induced behavioural sensitisation as well as its context-specific expression and the conditioned activity following its establishment.