The 5-Hydroxytryptamine2A Receptor Antagonist R-(+)-α-(2,3-Dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl-4-piperidinemethanol (M100907) Attenuates Impulsivity after Both Drug-Induced Disruption (Dizocilpine) and Enhancement (Antidepressant Drugs) of Differential-Reinforcement-of-Low-Rate 72-s Behavior in the Rat
| Autor: | Patrick L. Love, Paul A. Ardayfio, John T. Catlow, Mark J. Benvenga, Stephen F. Chaney, Steven P. Swanson, Gerard J. Marek |
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| Rok vydání: | 2008 |
| Předmět: |
medicine.drug_class
Pharmacology Impulsivity Receptors N-Methyl-D-Aspartate Piperidines medicine Animals Receptor Serotonin 5-HT2A Behavior Animal Tranylcypromine Psychotomimetic Receptor antagonist Antidepressive Agents Rats Fluorobenzenes Dizocilpine Molecular Medicine NMDA receptor Antidepressant Serotonin Antagonists Serotonin Dizocilpine Maleate medicine.symptom Psychology Reinforcement Psychology medicine.drug |
| Zdroj: | Journal of Pharmacology and Experimental Therapeutics. 327:891-897 |
| ISSN: | 1521-0103 0022-3565 |
| Popis: | Previous work has suggested that N-methyl-d-aspartate (NMDA) receptor antagonism and 5-hydroxytryptamine (5-HT)(2A) receptor blockade may enhance and attenuate, respectively, certain types of impulsivity mediated by corticothalamostriatal circuits. More specifically, past demonstrations of synergistic "antidepressant-like" effects of a 5-HT(2A) receptor antagonist and fluoxetine on differential-reinforcement-of-low-rate (DRL) 72-s schedule of operant reinforcement may speak to the role of 5-HT(2A) receptor blockade with respect to response inhibition as an important prefrontal cortical executive function relating to motor impulsivity. To examine the dynamic range over which 5-HT(2A) receptor blockade may exert effects on impulsivity, [R-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl-4-piperidinemethanol] (M100907) was examined both alone and in combination with the psychotomimetic NMDA receptor antagonist dizocilpine [e.g., (-)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate; MK-801] and two different antidepressants, the tricyclic antidepressant desmethylimipramine (DMI) and the monoamine oxidase inhibitor tranylcypromine in rats performing under a DRL 72-s schedule. MK-801 increased the response rate, decreased the number of reinforcers obtained, and exerted a leftward shift in the inter-response time (IRT) distribution as expected. A dose of M100907 that exerted minimal effect on DRL behavior by itself attenuated the psychotomimetic effects of MK-801. Extending previous M100907-fluoxetine observations, addition of a minimally active dose of M100907 to low doses of DMI and tranylcypromine enhanced the antidepressant-like effect of the antidepressants. Therefore, it may be that a tonic excitation of 5-HT(2A) receptors modulates impulsivity and function of corticothalamostriatal circuits over an extensive dynamic range. |
| Databáze: | OpenAIRE |
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