Temporal and dose-dependent differences in simultaneously-induced cocaine hypervigilance and conditioned-place-preference in marmoset monkeys.

Abstract

Although repeated exposure to cocaine can induce hypervigilance and conditioned-place-preference (CPP) in nonhuman primates (NHPs), more detailed analyses are warranted since the outcome can be influenced by different factors. We evaluated in marmoset monkeys (Callithrix penicillata): (1) the onset time-course and dose-dependent (3 or 7mg/kg; i.p.) profile of their hypervigilance and CPP response to repeated cocaine exposure; (2) whether these behavioral measures are still detectable after a 15-day no-drug period; (3) the relationship between their hypervigilance and CPP responses; and (4) if these behavioral changes correlate with pre- and post-drug behaviors (i.e., vigilance, locomotion, exploration), and/or first response to cocaine. Hypervigilance had a slow-onset, was only effective with the 7mg/kg dose of cocaine, lacked long-term conditioned effects and was not related to the initial cocaine response or pre-drug behaviors, regardless of the dose tested. CPP was promptly induced with the 3 and 7mg/kg doses, and had a dose-dependent long-term effect and negative correlation with pre-drug locomotion and exploration. Hypervigilance and CPP were not significantly correlated. Although hypervigilance and CPP were induced, they had distinct temporal and dose-dependent profiles, and were not equally co-expressed in the same marmoset. Also, in NHPs, pre-drug locomotion and exploration were predictive of the low-dose CPP response.