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 beta-adrenergic) antagonist propranolol. To test suggests that 5-HT inhibits ACh interneurons via one of the 5-HT1 receptor types. The 5HT1A 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 5-HT-ACh interaction may be involved in serotonergic treatment of depression.
Rada
P V
PV
Department of Psychology, Princeton University, NJ 08544-1010.
Mark
G P
GP
Hoebel
B G
BG
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002794:Choline / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology*; D007263:Infusions, Parenteral; D007395:Interneurons / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D012702:Serotonin Antagonists; D013997:Time Factors
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D005473:Fluoxetine; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D002794:Choline; D000109:Acetylcholine