In vivo modulation of acetylcholine in the nucleus accumbens of freely moving rats: I. 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 β-adrenergic) antagonist propranolol. To test β-adrenergic effects, it was found that a β-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-HT_1A agonist 8-OH-DPAT given systematically again decreased extracellular levels of ACh, and the effect was dose-dependent. The 5-HT_1A 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-HT_1A 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.