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Link to original content: http://www.ncbi.nlm.nih.gov/pubmed/15219766
Modulation of the stimulus effects of (+)amphetamine by the 5-HT6 antagonist MS-245 - PubMed Skip to main page content
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Comparative Study
. 2004 Jun;78(2):263-8.
doi: 10.1016/j.pbb.2004.03.017.

Modulation of the stimulus effects of (+)amphetamine by the 5-HT6 antagonist MS-245

Manik Pullagurla  1 , Tatiana Bondareva, Richard Young, Richard A Glennon
Affiliations
Comparative Study

Modulation of the stimulus effects of (+)amphetamine by the 5-HT6 antagonist MS-245

Manik Pullagurla et al. Pharmacol Biochem Behav. 2004 Jun.

Abstract

5-HT(6) serotonin receptors are distributed within some dopamine terminal regions in the brain leading to suggestions that they might influence dopaminergic function. In the present study, the 5-HT(6) antagonist 5-methoxy-N,N-dimethyl-N(1)-benzenesulfonyltryptamine (MS-245) was without effect when administered (3.0-7.5 mg/kg) to rats trained to discriminate (+)amphetamine (1.0 mg/kg) from saline vehicle in a two-lever drug discrimination task. Administered in combination, 0.3 mg/kg (i.e., the ED(50) dose) of (+)amphetamine plus 5.0 mg/kg of MS-245 elicited 95% amphetamine-appropriate responding. Similar studies were conducted using rats trained to discriminate cocaine (8.0 mg/kg) from saline vehicle, but a combination of 2.0 mg/kg (i.e., the ED(50) dose) of cocaine together with relatively low doses of MS-245 resulted in the percent response (approximately 50%) expected from administration of this dose of cocaine or in disruption of the animals' behavior. The present results confirm findings from other laboratories that 5-HT(6) antagonists can modulate amphetamine-induced behavioral actions, and further extend these findings to an example of a different structural class of 5-HT(6) antagonists and to a different behavioral paradigm. Taken together, the data suggest that 5-HT(6) serotonin agents (or at least MS-245) could have potential clinical application in therapies that involve modulation of dopamine neurotransmission.

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