The effect of 5-HT1A receptor ligands in a chronic mild stress model of depression

Antidepressant properties of 5-HT1A receptor ligands (the full agonist 8-OH-DPAT, the partial agonists ipsapirone and buspirone, and the selective antagonist WAY 100135) were studied in a chronic mild stress model of depression. In this model, rats subjected to a variety of mild stressors for a prolonged period of time show a substantial decrease in the consumption of a 1% sucrose solution (anhedonia), an effect being sensitive to repeated treatment with antidepressant drugs. In the present study we found that the stress-induced deficit in the sucrose intake was gradually reversed by chronic (3-5 weeks) administration of buspirone (2.5 and 5 mg/kg, i.p., b.i.d.) or WAY 100135 (10 mg/kg, s.c., b.i.d.), but not 8-OH-DPAT (0.5 mg/kg, s.c., b.i.d.) or ipsapirone (5 mg/kg i.p., b.i.d.). The magnitude of the effect of buspirone and WAY 100135 was comparable to that observed following similar administration of the antidepressant drugs imipramine (10 mg/kg i.p.) or citalopram (10 mg/kg i.p.). Increases in the sucrose intake following chronic treatment with buspirone, WAY 100135, imipramine and citalopram were specific to the stressed animals; the behaviour of control non-stressed animals was unchanged by any drug. These results suggest that buspirone and WAY 100135 may have antidepressant properties. Possible links between the anti-anhedonic effect of these drugs and their interaction with 5-HT1A receptors and/or the dopamine system are discussed.