IN-VIVO MODULATION OF ACETYLCHOLINE IN THE NUCLEUS-ACCUMBENS OF FREELY MOVING RATS .1. INHIBITION BY SEROTONIN

Microdialysis was used to characterize the effect of serotonergic input on cholinergic interneurons in the nucleus accumbens (NAC) of freely moving rats. Local infusion of 5-hydroxytryptamine (5-HT) or the serotonin reuptake blocker fluoxetine significantly decreased extracellular acetylcholine (ACh) in the NAC. This decrease in ACh was blocked by the 5-HT1 (and beta-adrenergic) antagonist propranolol. To test beta-adrenergic effects, it was found that a beta-adrenergic agonist isoproterenol had no measurable effect on extracellular ACh in the NAC. This suggests that 5-HT inhibits ACh interneurons via one of the 5-HT1 receptor types. The 5-HT1A agonist 8-OH-DPAT given systemically again decreased extracellular levels of ACh, and the effect was dose-dependent. The 5-HT1A effect was probably exerted in the NAC, because local infusion of 8-OH-DPAT mimicked systemic injections. These microdialysis results are similar to in vitro studies which suggest an inhibitory impact of 5-HT on ACh release in basal ganglia slices and homogenates. The decrease in extracellular ACh as measured in vivo is apparently mediated, at least in part, through a 5-HT1A receptor in the accumbens. Given the role of the NAC in behavior reinforcement, this 5HT-ACh interaction may be involved in serotonergic treatment of depression.