Antidepressant-like effects of buspirone mediated by the 5-HT1A post-synaptic receptors in the learned helplessness paradigm

Martin, Patrick; Tissier, Marie-Hélène; Adrien, Joëlle; Puech, Alain J.

doi:10.1016/0024-3205(91)90605-b

Cited by 39 publications

(23 citation statements)

References 18 publications

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“…Extensive studies showed that during 10-15 days after exposure to uncontrollable aversive events, helpless rats exhibit impairments in biochemical, physiological, hormonal and behavioural parameters somewhat similar to those of depressed patients (Sherman et al 1982;Willner 1986, 1990. The validity of this model is supported by many reports which confirmed that a large variety of antidepressant therapies are efficient in antagonizing the deficit in escape responding (Leshner et al 1979;Petty and Sherman 1979;Telner et al 1981;Martin et al 1986Martin et al , 1990Martin et al , 1991. Therefore, this model is of potential interest to gain insight into the neurobiological bases of depression and antidepressant therapy.…”

Section: Introductionmentioning

confidence: 77%

Antidepressant treatment in helpless rats: effect on the electrophysiological activity of raphe dorsalis serotonergic neurons

Maudhuit

Dangoumau

et al. 1997

Psychopharmacology

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Chronic treatment with antidepressants renders serotonergic neuronal firing less sensitive to the inhibitory effect of serotonin (5-HT) reuptake blockers in the rat, and this has been considered as a major correlate of the therapeutic action of these drugs. We investigated whether the same mechanisms could be evidenced in an experimental model of depression, the learned helplessness paradigm. Rats rendered helpless by a single session of inescapable electrical footshocks exhibit, for several days, depression-like behavioural deficits which can be reversed by sub-chronic, but not acute, treatment with antidepressants. Recording of serotonergic neurons in the dorsal raphe nucleus revealed that, under baseline conditions, the spontaneous firing was similar in helpless rats and in non-helpless controls. However, neurons in the former group exhibited an enhanced sensitivity to the inhibitory action of the 5-HT reuptake blocker, citalopram (ED50 = 0.18 +/- 0.02 mg/kg IV in helpless rats versus 0.27 +/- 0.03 mg/kg IV in controls, P < 0.05). Treatment with zimeldine during 3 consecutive days induced in both helpless and control rats, a decrease in the inhibitory response of serotonergic neurons to the citalopram challenge, which resulted in a normalization of the neuronal reactivity in the helpless group (ED50 = 0.31 +/- 0.03 mg/kg IV). Since this adaptive phenomenon parallels the behavioural improvement induced by the repeated administration of zimeldine and other antidepressants in helpless rats, it might be considered as a crucial event in the mechanism of therapeutic action of these drugs.

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Section: Introductionmentioning

confidence: 77%

Antidepressant treatment in helpless rats: effect on the electrophysiological activity of raphe dorsalis serotonergic neurons

Maudhuit

Dangoumau

et al. 1997

Psychopharmacology

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“…Buspirone is an anxiolytic drug, which as a partial 5-HT 1A receptor agonist also seems to augment the antidepressive effect of SSRIs (Blier et al 1997). Like the full 5-HT 1A receptor agonist 8-OH-DPAT, buspirone has an antidepressive profile in animal experiments (Marin et al 1991;Martin et al 1992). Doses were chosen based on known and wanted pharmacological effects in earlier studies.…”

Section: Discussionmentioning

confidence: 99%

Selective effects on NGFI-A, MR, GR and NGFI-B hippocampal mRNA expression after chronic treatment with different subclasses of antidepressants in the rat

et al. 2000

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There is a latency period of several weeks before the onset of clinical effect of antidepressant drugs. The detailed mechanisms underlying drug-induced adaptive neuronal changes are not known. To elucidate the involvement of changes in gene expression of candidate transcription factors, we treated rats for 21 days with buspirone, fluoxetine, 8-OH-DPAT and moclobemide. In situ hybridization was used to study mRNAs encoding NGFI-A, NGFI-B and the glucocorticoid receptors, MR and GR. NGFI-A mRNA expression increased profoundly in the hippocampal formation and the cerebral cortex after all drug treatments, especially after moclobemide treatment (77-122% increase); with the exception of buspirone. MR mRNA expression was induced in hippocampal CA1/CA2 subregions (27-37%) by all antidepressants, while moclobemide and 8-OH-DPAT significantly increased GR gene expression mainly in the CA1 region (31-44%). NGFI-B mRNA was significantly decreased in the hippocampal CA3 subfield (23%) and restrosplenial granular cortex (38%) by moclobemide treatment. There are selective effects of antidepressant drugs on specific transcription factors. These may be important for adaptive neuronal and neuroendocrine changes after antidepressant treatment including HPA axis negative feedback regulation.

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“…In addition, it has been reported that fluoxetine, after repeated treatment, prevents the escape deficit in this animal model also by activating 5-HT 1A receptors, although a different experimental protocol of the test was used (Gambarana et al 1995). Interestingly, the helpless behavior is reversed in the LH model by repeated treatment with putative 5-HT 1A agonists (Giral et al 1988) and it has been shown that their effect is due to the activation of postsynaptic 5-HT 1A receptors (Martin et al , 1991. Moreover, it has been reported that LH induction modifies in vivo cortical 5-HT release (Petty and Sherman 1983;Petty et al 1994) and that tricyclic antidepressants normalize this change ; such effects correlate with antidepressant concentrations in the anterior neocortex .…”

Section: Learned Helplessnessmentioning

confidence: 92%

BIMT 17: a putative antidepressant with a fast onset of action?

et al. 1997

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BIMT 17, the only compound reported to be a full 5-HT1A agonist and a 5-HT2A antagonist at the frontal cortex, was assessed in three animal paradigms sensitive to antidepressants in rats: olfactory bulbectomy (OB), differential-reinforcement-of-low rate 72-s (DRL 72-s) and learned helplessness (LH). In the OB rats, BIMT 17, given once daily for 14 consecutive days at an i.p. dose of 10 mg/kg, but not of 20 mg/kg, reduced the increase in ambulation of OB rats, 24 h after the last administration. In the DRL 72-s test, BIMT 17 had a different profile than imipramine. A single i.p. injection of 5, 10, 15 or 20 mg/kg BIMT 17, in contrast to the same doses of imipramine, did not affect response and reinforcement rate in DRL 72-s 1 h after the administration. On the other hand, BIMT 17 slightly shifted the peak of the interresponse time (IRT) distribution towards shorter IRT duration, while imipramine shifted the peak of the IRT distribution towards longer IRT duration. In the LH test, acute oral doses (36, 48 or 60 mg/kg) of BIMT 17, given 30 min before testing, reduced the number of escape failures in LH without altering the intertrial crossings. This effect was also induced by a repeated, but not single, administration with 8 or 16 mg/kg imipramine. The plasma levels following i.p. 10 or oral 48 mg/kg BIMT 17 were in the same range. These results indicate that BIMT 17 does not behave like imipramine in all the tests, and suggest that BIMT 17 acts through different mechanisms of action than imipramine. Only clinical trials will tell whether these mechanisms will be relevant, but if so, BIMT 17 might induce a faster onset of therapeutic activity.

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Antidepressant-like effects of buspirone mediated by the 5-HT1A post-synaptic receptors in the learned helplessness paradigm

Cited by 39 publications

References 18 publications

Antidepressant treatment in helpless rats: effect on the electrophysiological activity of raphe dorsalis serotonergic neurons

Antidepressant treatment in helpless rats: effect on the electrophysiological activity of raphe dorsalis serotonergic neurons

Selective effects on NGFI-A, MR, GR and NGFI-B hippocampal mRNA expression after chronic treatment with different subclasses of antidepressants in the rat

BIMT 17: a putative antidepressant with a fast onset of action?

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