title: Clozapine increases reward evaluation but not overall ingestive behaviour in rats licking for sucrose.
abstract: BACKGROUND
  Clozapine and the "atypical" antipsychotics are less prone than neuroleptics to induce extrapyramidal motor effects, worsening of the negative symptoms of schizophrenia and dysphoria. This is paralleled by preclinical evidence showing reduced suppression of behaviours aimed at the pursuit of reward, with increased measures of reward efficacy. Serotonin 5-HT2 receptors seem to play a role in determining this profile.
  
  
  OBJECTIVE
  We investigated the effects of clozapine on the microstructure of ingestive behaviour, which might reveal behavioural dimensions, such as reward evaluation and behavioural activation, which might be relevant in explaining its atypical profile. Moreover, we investigated the possibility that coadministration of the typical antipsychotic haloperidol and the 5-HT2A/2C receptor antagonist ritanserin might mimic clozapine effects.
  
  
  METHODS
  The effects of clozapine (0.5, 1 and 5 mg/kg) and of the coadministration of haloperidol (0.05 mg/kg) and ritanserin (0.5 and 3 mg/kg) have been examined on the microstructure of licking for a 10% sucrose solution in rats.
  
  
  RESULTS
  Clozapine failed to affect whole ingestion as revealed by the lack of effect on lick number. However, it increased reward evaluation at the dose of 1 mg/kg, as revealed by increased mean bout size. Haloperidol resulted in a decreased bout size. Ritanserin failed to exert any effects either alone or when coadministered with haloperidol.
  
  
  CONCLUSIONS
  The ability of clozapine to increase reward evaluation might contribute to explain its atypical profile both in the clinical setting and in preclinical studies. These results suggest that 5-HT2A/2C receptors are not involved in the observed effect.
authors.affiliation: Dipartimento di Scienze del Farmaco, Università di Sassari, Via Muroni 23/A, Sassari, Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: Galistu
authors.forename: Cristina
authors.initials: C
authors.lastname: Modde
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Pireddu
authors.forename: Flavia
authors.initials: F
authors.lastname: Franconi
authors.forename: Gino
authors.initials: G
authors.lastname: Serra
authors.forename: Paolo S
authors.initials: PS
authors.lastname: D'Aquila
mesh_terms: D059445:Anhedonia / Q000187:drug effects; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D003024:Clozapine / Q000494:pharmacology*; D003627:Data Interpretation, Statistical; D018492:Dopamine Antagonists / Q000494:pharmacology; D005247:Feeding Behavior / Q000187:drug effects*; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism; D012201:Reward; D016713:Ritanserin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D013395:Sucrose
chemical_list: D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D012702:Serotonin Antagonists; D016713:Ritanserin; D013395:Sucrose; D003024:Clozapine; D006220:Haloperidol