ArticlePsychopharmacology2009
Discriminative stimulus properties of the atypical antidepressant, mirtazapine, in rats: a pharmacological characterization.
Article in Psychopharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 14 citations in OpenAlex.
- Targeting of G-protein coupled receptors in sepsis.Pharmacology & therapeutics · 2020Review
- A Brief Review of the Pharmacology of Amitriptyline and Clinical Outcomes in Treating Fibromyalgia.Biomedicines · 2017Review
- Serotonin2C Receptors and the Motor Control of Oral Activity.Current neuropharmacology · 2013Article
- Mirtazapine alters cue-associated methamphetamine seeking in rats.Biological psychiatry · 2011Article
- Drug discrimination: 30 years of progress.Psychopharmacology · 2009Article
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Authors and funding
2 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
rationaleThough interoceptive properties of antidepressants have been described, discriminative stimulus (DS) properties of mirtazapine, which does not affect monoamine reuptake, remain uncharacterized.
objectivesThe objectives of the study are to train rats to recognize a mirtazapine DS, then perform substitution studies with other antidepressants and drugs acting at sites occupied by mirtazapine. MATERIALS AND
methodsUsing a two-lever, fixed-ratio 10 schedule, rats were trained to discriminate mirtazapine (2.5 mg/kg, i.p.) from saline.
resultsSessions, 63 +/- 8, were necessary to reach the criterion for 14 rats that all subsequently recognized (100%) mirtazapine at the training dose. Mirtazapine blocks serotonin (5-HT)(2C) receptors, and the 5-HT(2C) antagonists, SB242,084, SB243,213 and S32006, revealed dose-dependent and full (> or =80%) substitution at doses of 2.5, 2.5, and 0.63 mg/kg, respectively. By contrast, the 5-HT(2A) antagonists, MDL100,907 and SR46349-B, the 5-HT(2B) antagonist, SB204,741, and the 5-HT(3) antagonist, ondansetron, showed no significant substitution. Though mirtazapine indirectly recruits 5-HT(1A) receptors, the 5-HT(1A) agonists, buspirone and 8-OH-DPAT, did not substitute. Mirtazapine blocks alpha(2)-adrenoceptors, but several alpha(2)-adrenoceptor antagonists (yohimbine, RX821,002 and atipamezole) failed to substitute. Despite blockade by mirtazapine of histamine H(1) receptors, no substitution was seen with the selective H(1) antagonist, pyrilamine. Finally, the selective noradrenaline reuptake inhibitor, reboxetine (0.16), fully substituted for mirtazapine, whereas the 5-HT/noradrenaline reuptake inhibitors, duloxetine and S33005, several 5-HT reuptake inhibitors (citalopram, fluvoxamine, and paroxetine) and the dopamine reuptake inhibitors, bupropion and GBR12,935, did not substitute.
conclusionMirtazapine elicits a DS in rats for which selective antagonists at 5-HT(2C) receptors display dose-dependent substitution, whereas drugs acting at other sites recognized by mirtazapine are ineffective.
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