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: 4.82). 11/1995; 34(10):1305-10. DOI: 10.1016/0028-3908(95)00102-C
Source: PubMed

ABSTRACT 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.

Download full-text


Available from: Mariusz Papp, Aug 20, 2015
  • Source
    • "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 "
    [Show abstract] [Hide abstract]
    ABSTRACT: Modelling of complex psychiatric disorders, e.g., depression and schizophrenia, in animals is a major challenge, since they are characterized by certain disturbances in functions that are absolutely unique to humans. Furthermore, we still have not identified the genetic and neurobiological mechanisms, nor do we know precisely the circuits in the brain that function abnormally in mood and psychotic disorders. Consequently, the pharmacological treatments used are mostly variations on a theme that was started more than 50 years ago. Thus, progress in novel drug development with improved therapeutic efficacy would benefit greatly from improved animal models. Here, we review the available animal models of depression and schizophrenia and focus on the way that they respond to various types of potential candidate molecules, such as novel antidepressant or antipsychotic drugs, as an index of predictive validity. We conclude that the generation of convincing and useful animal models of mental illnesses could be a bridge to success in drug discovery.
    Cell and Tissue Research 08/2013; DOI:10.1007/s00441-013-1692-9 · 3.33 Impact Factor
  • Source
    • "The 5-HT 1A receptor agonists produce AD-like effects in rats responding under the DRL 72-s schedule (O'Donnell et al. 2005). Chronic treatment with the partial agonist buspirone produced AD-like effects in the CMS paradigm (Przegalinski et al. 1995) and chronic flesinoxan produced AD-like effects in the OB model (Cryan et al. 1997). Chronic administration of the 5-HT 1A receptor agonists 8-OH-DPAT or buspirone also reduces approach latencies in the NIH test and increases neurogenesis and survival of new neurons in the dentate gyrus after chronic treatment in rats and mice and (Banasr et al. 2004; Bodnoff et al. 1989; Santarelli et al. 2003). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Serotonin reuptake inhibitors (SSRIs) are effective in treating depression. Given the existence of different families and subtypes of 5-HT receptors, multiple 5-HT receptors may be involved in the antidepressant-like behavioral effects of SSRIs. Behavioral pharmacology studies investigating the role of 5-HT receptor subtypes in producing or blocking the effects of SSRIs were reviewed. Few animal behavior tests were available to support the original development of SSRIs. Since their development, a number of behavioral tests and models of depression have been developed that are sensitive to the effects of SSRIs, as well as to other types of antidepressant treatments. The rationale for the development and use of these tests is reviewed. Behavioral effects similar to those of SSRIs (antidepressant-like) have been produced by agonists at 5-HT(1A), 5-HT(1B), 5-HT(2C), 5-HT(4), and 5-HT(6) receptors. Also, antagonists at 5-HT(2A), 5-HT(2C), 5-HT(3), 5-HT(6), and 5-HT(7) receptors have been reported to produce antidepressant-like responses. Although it seems paradoxical that both agonists and antagonists at particular 5-HT receptors can produce antidepressant-like effects, they probably involve diverse neurochemical mechanisms. The behavioral effects of SSRIs and other antidepressants may also be augmented when 5-HT receptor agonists or antagonists are given in combination. The involvement of 5-HT receptors in the antidepressant-like effects of SSRIs is complex and involves the orchestration of stimulation and blockade at different 5-HT receptor subtypes. Individual 5-HT receptors provide opportunities for the development of a newer generation of antidepressants that may be more beneficial and effective than SSRIs.
    Psychopharmacology 02/2011; 213(2-3):265-87. DOI:10.1007/s00213-010-2097-z · 3.99 Impact Factor
  • Source
    • "In rats, chronic mild stress (CMS) induces anhedonia (Willner et al., 1992), a core symptom of depression that is defined as 'the decreased capacity to experience pleasure of any sort' (Fawcett et al., 1983). The CMS-induced reduction of intake or preference of sucrose is a robust effect (Willner et al., 1992; Willner, 2005) that can be returned to normal by chronic antidepressant treatment, including treatment with several selective serotonin reuptake inhibitors (Muscat et al., 1992; Przegalinski et al., 1995; Papp et al., 2002; Grippo et al., 2006). CMS also causes behavioural changes that resemble symptoms of depression, including decreased sexual and aggressive behaviour and decreased anxiety in the elevated plus maze, whereas social interaction was not affected (D'Aquila et al., 1994). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Several types of stress can increase vulnerability to developing depression. This depression may be caused by the effects of stress on the serotonergic system, which may make the system more vulnerable. The aim of this experiment was to evaluate whether chronic mild stress (CMS) resulted in long-lasting vulnerability of the serotonergic system, reflected by stronger behavioural responses to a serotonergic challenge with acute tryptophan depletion (ATD) several weeks after the CMS had ended. Male Wistar rats were exposed to 3 weeks of CMS followed by a 2-week resting period. CMS resulted in blunted weight gain and lower sucrose consumption. After the resting period, rats were repeatedly treated with a gelatin-based protein-carbohydrate mixture, either with or without L-tryptophan, to acutely challenge the serotonergic system and the rats were tested in several tests of anxiety-related and depression-related behaviour and memory. CMS and ATD both influenced behaviour on some tests, but overall this CMS procedure did not result in increased sensitivity to ATD, as there were no CMSxATD interaction effects on behaviour. In conclusion, CMS did not result in long-lasting vulnerability of the serotonergic system, measured by the behavioural response to ATD several weeks after the CMS had ended.
    Behavioural Pharmacology 11/2008; 19(7):706-15. DOI:10.1097/FBP.0b013e328315eced · 2.19 Impact Factor
Show more