THE ROLE OF MONOAMINE NEUROTRANSMITTER SYSTEMS IN THE NICOTINE DISCRIMINATIVE STIMULUS

Nicotine serves as a reinforcer and induces a robust discriminative st imulus which is primarily mediated by neuronal nicotinic receptors. As a secondary effect of nicotinic stimulation, nicotine elicits an enha nced release of the biogenic amine neurotransmitters dopamine, norepin ephrine and serotonin. In particular, compounds with dopaminergic acti vity have been reported to modify both the reinforcing and discriminat ive stimulus properties of nicotine. The present study examined a numb er of dopaminergic, noradrenergic and serotonergic compounds for their effectiveness in reproducing or modifying the stimulus properties of nicotine in rats. The non-selective dopamine agonists amphetamine, coc aine and apomorphine produced partial substitution for nicotine, while the selective D2/D3 agonists bromocriptine and 7-OH-DPAT and the dopa mine autoreceptor antagonist (+)-AJ-76 had little effect. The substitu tion of amphetamine for nicotine was not blocked by haloperidol, sugge sting a minimal role for D2 receptors in the nicotine-like discriminat ive effects of stimulants. The selective D1 agonist SKF 81297 produced partial substitution for nicotine (45% maximum), but further experime nts with the D1 antagonist SCH 23390 and with rats trained in a three- way discrimination procedure failed to support a primary role for this receptor in the substitution of dopaminergic drugs for nicotine. Fina lly, tests of compounds with effects on noradrenergic or serotonergic neurotransmission did not yield strong evidence for the involvement of these systems. Taken together, these data support earlier suggestions that activation of dopamine receptor subtypes plays a role in the nic otine-like stimulus properties of abused stimulants, but do not clearl y identify a single subtype that is uniquely responsible. (C) 1998 Els evier Science Ireland Ltd. All rights reserved.