Opposing roles for 5-HT2A and 5-HT2C receptors in the nucleus accumbens on inhibitory response control in the 5-choice serial reaction time task.
Serotonin (5-HT) is thought to play an important role in the regulation of behavioral inhibition. Studies manipulating 5-HT function in the rodent brain indicate that 5-HT receptors regulate distinct forms of impulsive behavior, including impulsive responding in the 5-choice serial reaction time task (5CSRTT). The present study investigates the loci of effects mediated by 5-HT(2A) and 5-HT(2C) receptors in attention and inhibitory response control using microinfusions targeted at the nucleus accumbens (NAc), prelimbic cortex (PL) and infralimbic cortex (IL). Rats were implanted with bilateral guide cannulas and received infusions of the selective 5-HT(2A) receptor antagonist M100907 (0.1 and 0.3 microg) or selective 5-HT(2C) receptor antagonist SB242084 (0.1 and 0.5 microg) immediately prior to testing. The results show that intra-NAc infusions of M100907 significantly decrease impulsive responding on the 5CSRTT and at the highest dose increased omissions as well. By contrast, infusions of SB242084 into the NAc selectively and dose-dependently increased impulsivity. Neither M100907 nor SB242084 significantly altered impulsive responding following either intra-PL or intra-IL administration. However, SB242084 significantly decreased omissions following intra-PL administration (0.5 microg only). These data reveal opposing effects on impulsivity following 5-HT(2A) and 5-HT(2C) blockade in the NAc. Our results suggest that the NAc, but not the PL or IL, is implicated in the mediation of the effects of M100907 and SB242084 on inhibitory response control during baseline 5CSRTT performance.
Department of Experimental Psychology, Behavioral and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
Emma S J
ES
Robinson
Jeffrey W
JW
Dalley
David E H
DE
Theobald
Jeffrey C
JC
Glennon
Marie A
MA
Pezze
Emily R
ER
Murphy
Trevor W
TW
Robbins
D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D001288:Attention / Q000187:drug effects / Q000502:physiology; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005464:Fluorobenzenes / Q000494:pharmacology; D007175:Impulsive Behavior / Q000378:metabolism / Q000503:physiopathology; D007211:Indoles / Q000494:pharmacology; D008032:Limbic System / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009483:Neuropsychological Tests; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology*; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects / Q000378:metabolism*; D044405:Receptor, Serotonin, 5-HT2C / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
C107820:6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline; D000631:Aminopyridines; D005464:Fluorobenzenes; D007211:Indoles; D010880:Piperidines; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D012702:Serotonin Antagonists; D012701:Serotonin; C079049:volinanserin