Effect of chronic administration of selective 5-hydroxytryptamine and noradrenaline uptake inhibitors on a putative index of 5-HT2C2B receptor function

doi:10.1016/0028-3908(94)90133-3

Neuropharmacology

Volume 33, Issue 12, December 1994, Pages 1581-1588

https://doi.org/10.1016/0028-3908(94)90133-3 Get rights and content

Abstract

Chronic treatment with selective 5-HT reuptake inhibitors (SSRI) are therapeutic in obsessive compulsive disorder, depression, anxiety, bulimia nervosa and migraine. In the present study the possibility that SSRI's act by desensitizing 5-HT_2C/5-HT_2B receptors was assessed using a putative in vivo model of 5-HT_2C/5-HT_2B receptor function, mCPP-induced hypolocomotion. mCPP (2,4 and 6 mg/kg i.p. 20 min pretest) reduced locomotion and rears in rats treated acutely or chronically with saline. Acute oral administration of the SSRI's fluoxetine (10 mg/kg), paroxetine (10 mg/kg), or clomipramine (70 mg/kg) or the noradrenaline reuptake inhibitor, desipramine (10 mg/kg), all 1 hr pretest, did not prevent mCPP-induced hypolocomotion. In contrast, chronic treatment with the SSRI's paroxetine and fluoxetine (both 10 mg/kg p.o. daily × 21 days), significantly attenuated the effect of mCPP (4 and 6 mg/kg i.p.) on locomotion and rears 24 hr after the last pretreatment dose. Chronic clomipramine (70 mg/kg p.o. daily × 21 days) also significantly attenuated the effect of mCPP (4 mg/kg i.p.) on rears and tended to reduce the hypolocomotor response. However, chronic treatment with desipramine, (10 mg/kg p.o.daily × 21) had no effect on any of the parameters measured. As chronic fluoxetine and paroxetine did not reduce brain mCPP levels (determined by HPLC 30 min after 4 mg/kg i.p.) the results suggest that chronic SSRI's, but not desipramine, reduce 5-HT_2C/5-HT/_2B receptor responsivity. If this occurs in man, it may mediate or contribute to their reported therapeutic efficacy in depression, anxiety, bulimia, migraine and alcoholism. It may also be of particular relevance to their unique efficacy in OCD.

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Serotonin regulates many physiological processes including sleep, appetite, and mood. Thus, serotonergic system is an important target in the treatment of psychiatric disorders, such as major depression and anxiety. This natural neurotransmitter interacts with 7 families of its receptors (5-HT1-7), which cause a variety of pharmacological effects. Using genetically modified animals and selective or preferential agonists and antagonist, numerous studies demonstrated the involvement of almost all serotonin receptor subtypes in antidepressant- or anxiolytic-like effects. In this review, based on animal studies, we discuss the possible involvement of serotonin receptor subtypes in depression and anxiety.
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Effect of chronic administration of selective 5-hydroxytryptamine and noradrenaline uptake inhibitors on a putative index of 5-HT2C2B receptor function

Abstract

Eur. J. Pharmac.

Neuropharmacology

Eur. J. Pharmac.

Eur. J. Pharmac.

FEBS Lett.

Biochem. Pharmac.

Molec. Brain Res.

FEBS Lett.

Psychiatry Res.

Biol. Psychiat.

Differential effects of clomipramine given locally or systemically on extracellular 5-hydroxytryptamine in raphe nuclei and frontal cortex

Naunyn Schmiedeberg s Archs Pharmac.

Drug-induced priapism. Its aetiology, incidence and treatment

Med. Toxic. Adverse Drug Exp.

Attenuation of 5-HT1A and 5-HT2 but not 5-HT1C receptor mediated behaviour in rats following chronic treatment with 5-HT receptor agonists, antagonists or anti-depressants

Psychopharmacology

The antimigraine drugs ergotamine and dihydroergotamine are potent 5-HT1C receptor agonists in piglet choroid plexus

Br. J. Pharmac.

Monoamine oxidase inhibitors increase preferentially extracellular 5-hydroxytryptamine in the midbrain raphe nuclei. A brain microdialysis study in the awake rat

Naunyn Schmiedeberg's Archs Pharmac.

Characterization of 5-hydroxytryptamine receptors in rat stomach fundus

J. Pharmac. Exp. Ther.

Relative efficacies of piperazines at the phosphoinositide hydrolysis-linked serotonergic (5-HT2 and 5-HT1C) receptors

J. Pharmac. Exp. Ther.

Effect of chronic administration of antidepressant drugs on 5-HT2-mediated behaviour in the rat following noradrenergic or serotonergic denervation

J. Neural Transm.

Sertraline as a treatment for panic disorder

Neuropsychpharmacology

Serotonergic and noradrenergic sensitivity in obsessive-compulsive disorder: behavioural findings

Am. J. Psychiat.

Effects of chronic fluoxetine treatment on behaviour and neuroendocrine responses to meta-chlorophenylpiperazine in patients and healthy subjects

Psychiat. Res.

Serotonin function in obsessive-compulsive disorder. Behavioural and neuroendocrine responses to oral m-chlorophenylpiperazine and fenfluramine in patients and healthy volunteers

Arch. Gen. Psychiat.

Chronic fluoxetine treatment upregulates 5-HT uptake sites and 5-HT2 receptors in rat brain: an autoradiological study

Synapse

New pharmacological approaches to obsessive compulsive disorder

J. Clin. Psychiat.

Neuroendocrine evidence for serotonin receptor supersensitivity in patients with panic disorder

Psychopharmacology

Effect of chronic administration of selective 5-hydroxytryptamine and noradrenaline uptake inhibitors on a putative index of 5-HT_{$2C 2B$} receptor function

Attenuation of 5-HT_1A and 5-HT₂ but not 5-HT_1C receptor mediated behaviour in rats following chronic treatment with 5-HT receptor agonists, antagonists or anti-depressants

The antimigraine drugs ergotamine and dihydroergotamine are potent 5-HT_1C receptor agonists in piglet choroid plexus

Relative efficacies of piperazines at the phosphoinositide hydrolysis-linked serotonergic (5-HT₂ and 5-HT_1C) receptors

Effect of chronic administration of antidepressant drugs on 5-HT₂-mediated behaviour in the rat following noradrenergic or serotonergic denervation

Chronic fluoxetine treatment upregulates 5-HT uptake sites and 5-HT₂ receptors in rat brain: an autoradiological study