A novel neuropeptide regulator of behavioral sensitization to cocaine

Aims: We have previously demonstrated in male rats that repeated exposure to amphetamine (AMPH) from earlyto midadolescence [postnatal day (P) 27 to 45] persistently alters the function of dopamine D1 receptors in the medial prefrontal cortex (mPFC). Here, we determined if this functional change was associated with altered D1 expression in the mPFC and nucleus accumbens (NAc), whether the timing of drug exposure (earlyvs. late-adolescence) influenced drug-induced plasticity, and whether adolescent AMPH exposure altered anxietyand depression-like behavior. Methods: Male and female Sprague-Dawley rats (n=78) were treatedwith salineor3mg/kgAMPH(i.p.) everyotherday (10 injections total) during early (P27 to 45) or late adolescence (P37 to 55). Sucrose preference (SP) tests were then performed after 1, 7, and 21 days of withdrawal. For each test, the consumption of water and 1% sucrose was measured for 48h. Before the last SP test, anxietylike behavior was assessed by measuring activity in an open-field arena and an elevated plus maze (EPM). Rats were sacrificed after finishing the last SP test, the mPFC and NAc were collected, and D1 protein levels were measured using Western blot analysis. Results: AMPH exposure induced a decrease of SP during the first test. In the EPM, early, but not late, AMPH treatment increased time spent in open arms. Lastly, we found decreased D1 levels in the mPFC following early AMPH exposure. Conclusions: Our preliminary findings suggest that adolescent AMPH exposure induces lasting changes in mPFC D1 expression, which may play a role in the anhedonia and “risk taking” behavior we observed. Importantly, these drug-induced changes are more robust following earlycompared to late-adolescent exposure, suggesting a heightened vulnerability to AMPH in early adolescence. Financial support: This study is supported byNIH (DA 029815).