The influence of cocaine self-administration on in vivo dopamine and acetylcholine neurotransmission in rat caudate-putamen.

Presynaptic dopamine and acetylcholine transmission in the anteroventral (limbic) caudate-putamen were studied by microdialysis in freely moving rats during cocaine self-administration sessions. Acute cocaine exposure elevated dopamine (DA) overflow in drug-naive animals. However, during repeated cocaine administration, the drug-induced elevation of DA was attenuated in animals previously exposed (during the prior 9 days) to cocaine. The diminished dopamine response in repeatedly treated animals while self-administering cocaine was speculated to be due to increased activity of DA transport carrier and/or supersensitive receptors modulating DA release. During repeated cocaine administration, extracellular acetylcholine levels in animals previously exposed to cocaine were found to be significantly decreased compared with controls. The findings of the study may suggest a functional development of supersensitive DA receptors postsynaptic to the DA terminal (located on cholinergic neurons) as a consequence of previous cocaine exposure. Such supersensitivity would allow for a reduced DA signal to be amplified at the postsynaptic level during repeated cocaine self-administration.