Effects of the antidepressant trazodone, a 5-HT(2A/2C) receptor antagonist, on dopamine-dependent behaviors in rats
by
Balsara JJ, Jadhav SA, Gaonkar RK,
Gaikwad RV, Jadhav JH.
Department of Pharmacology,
Krishna Institute of Medical Sciences,
Karad, Maharashtra, 415 110, India,
klgaonkar@sancharnet.in.
Psychopharmacology (Berl). 2004 Dec 22

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.

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