科研之友
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摘要
Asenapine is a new antipsychotic drug that induces a long-lasting behavioral sensitization in adult rats. The present study investigated the developmental impacts of adolescent asenapine treatment on drug sensitivity and on 3 proteins implicated in the action of antipsychotic drugs (i.e. brain-derived neurotrophic factor (BDNF), dopamine D-2 receptor, and Delta FosB) in adulthood. Male adolescent Sprague-Dawley rats (postnatal days, P43-48) were first treated with asenapine (0.05, 0.10 or 0.20 mg/kg, sc) and tested in the conditioned avoidance or PCP (2.0 mg/kg, sc)-induced hyperlocomotion tasks for 5 days. After they became adults (similar to P 76), asenapine sensitization was assessed in a single avoidance or PCP-induced hyperlocomotion challenge test with all rats being injected with asenapine (0.10 mg/kg, sc). Rats were then sacrificed 1 day later and BDNF, D-2 and Delta FosB in the prefrontal cortex, striatum and hippocampus were examined using Western blotting. In adolescence, repeated asenapine treatment produced a persistent and dose-dependent inhibition of avoidance response, spontaneous motor activity and PCP-induced hyperlocomotion. In the asenapine challenge test, adult rats treated with asenapine (0.10 and 0.20 mg/kg) in adolescence made significantly fewer avoidance responses and showed a stronger inhibition of spontaneous motor activity than those previously treated with saline. However, no group difference in the levels of BDNF, D-2 and Delta FosB expression was found. These findings suggest that although adolescent asenapine treatment for a short period of time induces a robust behavioral sensitization that persists into adulthood, such a long-term effect is not likely to be mediated by BDNF, D-2 and Delta FosB.
