title: Effects of 5-HT1A, 5-HT2Aand 5-HT2Creceptor agonists and antagonists on responding for a conditioned reinforcer and its enhancement by methylphenidate.
abstract: These experiments examined the effects of selective 5-HT1A, 5-HT2Aand 5-HT2Creceptor ligands on responding for a conditioned reinforcer (CRf). Effects of these ligands were measured under basal conditions and following elevated dopamine (DA) activity produced by the DA reuptake inhibitor methylphenidate.
  
  
  
  Water-restricted rats learned to associate a conditioned stimulus (CS) with water in operant chambers. Subsequently, two response levers were made available; responding on one lever delivered the CS (now a CRf), while responding on the second lever had no consequences. The effects of agonist and antagonists of 5-HT1A(8-hydroxy-2(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT) and N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide (WAY100635)), 5-HT2A(DOI and M100907) and 5-HT2C(Ro60-0175 and SB242084) receptors on responding were examined alone, as well as in the presence of methylphenidate.
  
  
  
  Responding for a CRf was reduced by the agonists 8-OH-DPAT, DOI and Ro60-0175. 8-OH-DPAT also reduced responding for water and seemed to impair responding in a non-specific fashion. None of the receptor antagonists affected responding. Methylphenidate dose-dependently enhanced responding for a CRf, and this was attenuated by DOI and Ro60-0175. Conversely, the 5-HT2Creceptor antagonist SB242084 potentiated the effect of methylphenidate.
  
  
  
  No evidence was found for a behaviourally selective effect of 5-HT1Areceptor ligands on responding for a CRf. Activation of 5-HT2Areceptors selectively inhibits responding for a CRf. 5-HT2Creceptor ligands exerted bidirectional modulation of responding for a CRf, especially when DA activity was increased. This indicates that 5-HT2Creceptor activity is an important modulator of DA-dependent reward-related behaviours.
authors.affiliation: Section of Biopsychology and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, M5T 1R8, Canada. Paul.Fletcher@camh.ca.|Department of Psychiatry, University of Toronto, Toronto, Canada. Paul.Fletcher@camh.ca.|Department of Psychology, University of Toronto, Toronto, Canada. Paul.Fletcher@camh.ca.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Fletcher
authors.affiliation: Section of Biopsychology and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, M5T 1R8, Canada.|Department of Psychiatry, University of Toronto, Toronto, Canada.
authors.forename: Fiona D
authors.initials: FD
authors.lastname: Zeeb
authors.affiliation: Section of Biopsychology and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, M5T 1R8, Canada.|Department of Psychology, University of Toronto, Toronto, Canada.
authors.forename: Caleb J
authors.initials: CJ
authors.lastname: Browne
authors.affiliation: Department of Pharmacology, University of Toronto, Toronto, Canada.|InterVivo Solutions Inc., Toronto, Canada.
authors.forename: Guy A
authors.initials: GA
authors.lastname: Higgins
authors.affiliation: Section of Biopsychology and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, M5T 1R8, Canada.
authors.forename: Ashlie D
authors.initials: AD
authors.lastname: Soko
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000631:Aminopyridines / Q000494:pharmacology; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects*; D005464:Fluorobenzenes / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D044282:Receptor, Serotonin, 5-HT1A; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D012054:Reinforcement, Psychology; D058825:Serotonin 5-HT1 Receptor Agonists / Q000494:pharmacology; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
chemical_list: C107820:6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline; D000631:Aminopyridines; D000662:Amphetamines; D005464:Fluorobenzenes; D007211:Indoles; D010879:Piperazines; D010880:Piperidines; D011725:Pyridines; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D008774:Methylphenidate; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C079049:volinanserin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine
keywords: 5-HT1A receptors; 5-HT2A receptors; 5-HT2C receptors; Conditioned reinforcer; Methylphenidate; Serotonin