5-HT2 receptor antagonism reduces hyperactivity induced by amphetamine, cocaine, and MK-801 but not D1 agonist C-APB
| Autor: | Claire L Heron-Maxwell, Gillian Shaw, Michael F O'Neill |
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| Rok vydání: | 1999 |
| Předmět: |
Agonist
medicine.medical_specialty Indoles medicine.drug_class Clinical Biochemistry Aminopyridines Ritanserin Pharmacology Motor Activity Toxicology Biochemistry Behavioral Neuroscience Mice Cocaine Piperidines Dopamine Internal medicine medicine Animals Drug Interactions Amphetamine Biological Psychiatry 5-HT receptor Chemistry 5-HT2 receptor Dopaminergic Benzazepines Fluorobenzenes Endocrinology Dopamine receptor Dopamine Agonists Female Serotonin Antagonists Dizocilpine Maleate medicine.drug |
| Zdroj: | Pharmacology, biochemistry, and behavior. 63(2) |
| ISSN: | 0091-3057 |
| Popis: | The hyperlocomotion induced by the noncompetitive NMDA antagonist MK-801 (0.3 mg/kg SC) in mice was attenuated by the nonselective 5-HT2 antagonist ritanserin (0.12 and 0.25 mg/kg SC) and by the 5-HT2A selective antagonist MDL100907 (0.05 and 0.1 mg/kg SC). SB242084 (0.25-1.0 mg/kg), a selective 5-HT(2C) antagonist, had no effect on MK-801-induced hyperactivity. These same doses of ritanserin and MDL100907 reduced the hyperactivity induced by cocaine (10 mg/ kg). Amphetamine (2.5 mg/kg SC) induced hyperlocomotion that was also attenuated by ritanserin (0.064).25 mg/kg SC). The hyperlocomotion induced by the D1 agonist C-APB (1.0 mg/kg) is not altered by pretreatment with ritanserin or MDL100907. This suggests that compounds that increase locomotor activity via indirectly increasing dopaminergic activity (either by increased release or blockade of reuptake) require the activation of a 5-HT2A receptor. Activity of compounds that act directly at the postsynaptic dopamine receptors such as C-APB is not dependent on such a mechanism. This suggests a selective involvement of 5-HT2A receptors but not 5-HT2c receptors in the mediation of the behavioral effects of compounds that increase synaptic concentration of dopamine but not directly acting agonists. This implies that the 5-HT2A receptors modulate elevation of extracellular dopamine, not the postsynaptic sensitivity of dopamine neurons. |
| Databáze: | OpenAIRE |
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