Intravenous haloperidol and cocaine alter the distribution of T CD3⁺CD4⁺, non-T/NK and NKT cells in rats

The modulation of dopamine transmission evokes strong behavioural effects that can be achieved by commonly used psychoactive drugs such as haloperidol or cocaine. Cocaine non-specifically increases dopamine transmission by blocking dopamine active transporter (DAT) and evokes behavioural arousal, whereas haloperidol is a non-specific D2-like dopamine receptor antagonist with sedative effects. Interestingly, dopamine has been found to affect immune cells in addition to its action in the central nervous system. Here, we address the possible interactions between haloperidol and cocaine and their effects on both immune cells and behaviour in freely moving rats. We use an intravenous model of haloperidol and binge cocaine administration to evaluate the drugs' impact on the distribution of lymphocyte subsets in both the peripheral blood and the spleen. We assess the drugs' behavioural effects by measuring locomotor activity. Cocaine evoked a pronounced locomotor response and stereotypic behaviours, both of which were completely blocked after pretreatment with haloperidol. The results suggest that blood lymphopenia, which was induced by haloperidol and cocaine (except for natural killer T cells), is independent of D2-like dopaminergic activity and most likely results from the massive secretion of corticosterone. Haloperidol pretreatment prevented the cocaine-induced decrease in NKT cell numbers. Moreover, the increased systemic D2-like dopaminergic activity after cocaine administration is a significant factor in retaining T CD3⁺CD4⁺ lymphocytes and non-T/NK CD45RA⁺ cells in the spleen.