Sexual cues influence cocaine-induced locomotion, anxiety and the immunoreactivity of oestrogen receptor alpha and tyrosine hydroxylase in both sexes.

Dyadic physical social interaction influences cocaine-seeking behaviour, although whether limited sexual cues (LSC) from an opposite-sex partner influence the behavioural responses to cocaine is unclear. We investigated this issue using a cylindrical wire cage containing a stimulus mouse; the subject mouse (of the opposite sex) had access to this stimulus mouse during a "binge" injection pattern (injected with cocaine or saline vehicle twice a day at 6-hour intervals). Following the second injection, locomotion and anxiety-like behaviours were examined using the open-field and elevated plus maze test, at the same time as oestrogen receptor (ER)α and tyrosine hydroxylase (TH) immunoreactivities were also examined. The data indicate that LSC enhanced cocaine-stimulated locomotion in both sexes and inhibited the levels of anxiety caused by cocaine in males only. Accompanying these changes, the interaction between LSC and cocaine altered ERα immunoreactivity in the ventral medial nuclei of the hypothalamus (VMH) and medial amygdaloid nucleus (MeA) of males, whereas such interaction effects occurred in the VMH, MeA, arcuate nucleus (AR), bed nucleus of the stria terminalis (BNST) and lateral septum (LS) of females. LSC increased cocaine-induced ERα immunoreactivity in the VMH in males and reduced cocaine-induced ERα immunoreactivity in the AR and LS in females. LSC up-regulated cocaine-induced increases in ventral tegmental area (VTA) TH immunoreactivity in females only. Our present data suggest that interactions between LSC and cocaine led to changes in ERα and TH immunoreactivity in a brain region-specific manner, which showed subtle differences in both sexes. The effects of LSC-mediated cocaine-induced locomotion and anxiety may be associated with alterations in ERα and dopamine activation.