Antagonism at 5-HT(2A) receptors potentiates the effect of haloperidol in a conditioned avoidance response task in rats

Pharmacology, Biochemistry, and Behavior
M G WadenbergP B Hicks

Abstract

High affinity for serotonin-2A (5-HT(2A)) over dopamine (DA) D(2) receptors is a leading hypothesis for clozapine's favorable therapeutic profile. Recent preclinical studies also indicate that a sufficient antipsychotic effect might be obtained by a combined high 5-HT(2A)/low D(2) receptor blockade. Thus, addition of a 5-HT(2A) receptor antagonist to an ineffective dose of a D(2) receptor antagonist produces a robust antipsychotic-like effect in the conditioned avoidance response (CAR) test. Electrophysiological and biochemical studies also show that 5-HT(2A) receptor antagonists can confer an atypical (clozapine-like) profile on a D(2) receptor antagonist. Improved therapeutic efficacy by adjunctive 5-HT(2A) receptor antagonist treatment to a traditional D(2) receptor blocking regimen has been suggested. However, the ability of 5-HT(2A) receptor blockade to protect against, or ameliorate, parkinsonian symptoms still remains unclear. Using the CAR and the catalepsy (CAT) tests as indices for antipsychotic activity and extrapyramidal side effect (EPS) liability, respectively, the effects of the selective 5-HT(2A) receptor antagonist MDL 100,907 in combination with the DA D(2) receptor antagonists haloperidol or raclopride were s...Continue Reading

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Citations

Jun 24, 2006·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Faïza BenaliouadPierre-Paul Rompré
Sep 13, 2014·Current Behavioral Neuroscience Reports·Alexandra D ForrestSteven J Siegel
Jun 24, 2008·Network : Computation in Neural Systems·Michael MoutoussisPeter Dayan
Jul 20, 2006·Expert Opinion on Therapeutic Targets·Philip Seeman
Sep 20, 2012·Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco·Allison C Hoffman, Sarah E Evans
Nov 7, 2003·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Alasdair M BarrMark A Geyer
Dec 14, 2006·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Sridhar NatesanShitij Kapur
Dec 2, 2005·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Sridhar NatesanShitij Kapur
Nov 19, 2019·Behavioural Brain Research·Amanda M HaskellRichard J Servatius

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