title: Effects of the antidepressant trazodone, a 5-HT 2A/2C receptor antagonist, on dopamine-dependent behaviors in rats.
abstract: BACKGROUND
  5-Hydroxytryptamine, via stimulation of 5-HT 2C receptors, exerts a tonic inhibitory influence on dopaminergic neurotransmission, whereas activation of 5-HT 2A receptors enhances stimulated DAergic neurotransmission. The antidepressant trazodone is a 5-HT 2A/2C receptor antagonist.
  
  
  OBJECTIVE
  To evaluate the effect of trazodone treatment on behaviors dependent on the functional status of the nigrostriatal DAergic system.
  
  
  METHODS
  The effect of pretreatment with trazodone on dexamphetamine- and apomorphine-induced oral stereotypies, on catalepsy induced by haloperidol and apomorphine (0.05 mg/kg, i.p.), on ergometrine-induced wet dog shake (WDS) behavior and fluoxetine-induced penile erections was studied in rats. We also investigated whether trazodone induces catalepsy in rats.
  
  
  RESULTS
  Trazodone at 2.5-20 mg/kg i.p. did not induce catalepsy, and did not antagonize apomorphine (1.5 and 3 mg/kg) stereotypy and apomorphine (0.05 mg/kg)-induced catalepsy. However, pretreatment with 5, 10 and 20 mg/kg i.p. trazodone enhanced dexamphetamine stereotypy, and antagonized haloperidol catalepsy, ergometrine-induced WDS behavior and fluoxetine-induced penile erections. Trazodone at 30, 40 and 50 mg/kg i.p. induced catalepsy and antagonized apomorphine and dexamphetamine stereotypies.
  
  
  CONCLUSIONS
  Our results indicate that trazodone at 2.5-20 mg/kg does not block pre- and postsynaptic striatal D2 DA receptors, while at 30, 40 and 50 mg/kg it blocks postsynaptic striatal D2 DA receptors. Furthermore, at 5, 10 and 20 mg/kg, trazodone blocks 5-HT 2A and 5-HT 2C receptors. We suggest that trazodone (5, 10 and 20 mg/kg), by blocking the 5-HT 2C receptors, releases the nigrostriatal DAergic neurons from tonic inhibition caused by 5-HT, and thereby potentiates dexamphetamine stereotypy and antagonizes haloperidol catalepsy.
authors.affiliation: Department of Pharmacology, Krishna Institute of Medical Sciences, Karad, Maharashtra, 415 110, India.
authors.forename: Jehangir J
authors.initials: JJ
authors.lastname: Balsara
authors.forename: Sujata A
authors.initials: SA
authors.lastname: Jadhav
authors.forename: Rajani K
authors.initials: RK
authors.lastname: Gaonkar
authors.forename: Ramona V
authors.initials: RV
authors.lastname: Gaikwad
authors.forename: Jagdish H
authors.initials: JH
authors.lastname: Jadhav
mesh_terms: D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology* / Q000633:toxicity; D002375:Catalepsy / Q000139:chemically induced / Q000378:metabolism; D004298:Dopamine / Q000502:physiology*; D065127:Dopamine D2 Receptor Antagonists; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A / Q000502:physiology; D044405:Receptor, Serotonin, 5-HT2C / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D013239:Stereotyped Behavior / Q000187:drug effects* / Q000502:physiology; D014196:Trazodone / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D018687:Antidepressive Agents, Second-Generation; D065127:Dopamine D2 Receptor Antagonists; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D017448:Receptors, Dopamine D2; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists; D004298:Dopamine; D014196:Trazodone