Cocaine-induced behavioral sensitization in preweanling and adult rats: effects of a single drug-environment pairing.

RATIONALE: Adult rats typically exhibit more robust behavioral sensitization than do preweanling rats. A possible explanation for this age-dependent difference is that environmental context may have relatively less impact on the psychostimulant-induced behaviors of preweanling rats. OBJECTIVE: The purpose of this study was to assess the importance of environmental context for the development of cocaine-induced sensitization in preweanling and adult rats. MATERIALS AND METHODS: On postnatal day (PD) 19 or PD 79, rats in the context-dependent condition were injected with 30 mg/kg cocaine immediately before being placed in a novel test chamber for 30 min. The same rats were then injected with saline 30 min after being returned to the home cage. Rats in the context-independent condition were injected with saline before being placed in the novel chamber and cocaine in the home age. Control rats were injected with saline at both time points. One day later, adult and preweanling rats were challenged with saline or 10 mg/kg cocaine (experiment 1), or preweanling rats were challenged with 5, 20, or 30 mg/kg cocaine (experiment 2). After being injected, rats were placed in the test chamber, and behavior was measured for 60 min. RESULTS: Adult rats showed context-dependent locomotor sensitization and conditioned activity, with females exhibiting more locomotor activity than males. Preweanling rats did not exhibit conditioned activity, but they showed robust context-dependent and context-independent sensitization when challenged with 10-30 mg/kg cocaine. CONCLUSIONS: Context did not influence the expression of behavioral sensitization in preweanling rats, suggesting that deficits in associative or memory processes may be responsible for age-dependent differences in behavioral sensitization and conditioned activity.

Effects of a partial D2-like receptor agonist on striatal dopamine autoreceptor functioning in preweanling rats.

There is evidence that partial D2-like dopamine agonists (e.g., terguride) may not affect D2-like postsynaptic receptors in an adult-typical manner during the preweanling period. To determine whether synthesis modulating dopamine autoreceptors are also affected in an adult atypical manner by partial D2-like agonists, preweanling rats were treated either acutely or repeatedly with reserpine (low dopaminergic tone) or vehicle (high dopaminergic tone). The ability of terguride, quinpirole (a full D2-like agonist), or haloperidol (a D2-like antagonist) to alter striatal DOPA accumulation was assessed after NSD-1015 treatment on postnatal day (PD) 21. In a separate set of experiments, terguride's ability to modulate dopamine synthesis was assessed in rats treated with the nerve impulse flow inhibitor gamma-butyrolactone (GBL). Results showed that both terguride and quinpirole reduced striatal DOPA accumulation during a state of low dopaminergic tone (i.e., after reserpine pretreatment). During a state of high dopaminergic tone (i.e., after vehicle pretreatment), terguride had similar effects as haloperidol and increased DOPA accumulation. Terguride, like quinpirole, partially inhibited the GBL-induced increase in striatal DOPA accumulation. When considered together, these results indicate that synthesis modulating D2-like autoreceptors are functional during the late preweanling period, and they respond in an adult-typical manner to a partial D2-like agonist.