Effects of the antidepressant trazodone, a 5-HT 2A/2C receptor antagonist, on dopamine-dependent behaviors in rats.

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Citation

Balsara JJ, Jadhav SA, Gaonkar RK, Gaikwad RV, Jadhav JH

Effects of the antidepressant trazodone, a 5-HT 2A/2C receptor antagonist, on dopamine-dependent behaviors in rats.

Psychopharmacology (Berl). 2005 May;179(3):597-605. doi: 10.1007/s00213-004-2095-0. Epub 2004 Dec 22.

PubMed ID
15614572 [ View in PubMed
]
Abstract

RATIONALE: 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. OBJECTIVES: 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.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
Trazodone5-hydroxytryptamine receptor 2AProteinHumans
Yes
Antagonist
Details
Trazodone5-hydroxytryptamine receptor 2CProteinHumans
Yes
Agonist
Details