The effect of 5-HT 1A receptor ligands in a chronic mild stress model of depression

Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland.
Neuropharmacology (Impact Factor: 5.11). 11/1995; 34(10):1305-10. DOI: 10.1016/0028-3908(95)00102-C
Source: PubMed


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.

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    • "Fluoxetine (Jindal et al. 2013; Muscat et al. 1992; Mutlu et al. 2012), maprotiline (Muscat et al. 1992), minaserin (Cheeta et al. 1994), imipramine (Marston et al. 2011; Norman et al. 2012; Papp et al. 1996; Przegalinski et al. 1995), buspirone (Papp et al. 1996; Przegalinski et al. 1995), ipsapirone (Przegalinski et al. 1995), agomelatine (Bourin et al. 2004; Dagyte et al. 2011), risperidon (Marston et al. 2011), citalopram (Herrera-Perez et al. 2010; Przegalinski et al. 1995), escitalopram (Christensen et al. 2012), tianeptine (Mutlu et al. 2012) Social stress— repeated defeat "
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    • "BUS showed reversal of stress induced deficit in the sucrose intake (anhedonia), a major symptom of depression.[14] Further it exhibited significant anxiolytic activity in Vogel's and the open-field tests and novelty-suppressed feeding in food-deprived rats.[1516] It indicated significant mood regulating activity of BUS possibly by modulating 5-HT1A receptors in brain areas. "
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