Tolerance and cross-tolerance to the activating effects of 3,4-methylenedioxymethamphetamine and a 5-hydroxytryptamine1B agonist.
Previous studies indicate that 3,4-methylenedioxymethamphetamine (MDMA) produces locomotor hyperactivity in rats by increasing the presynaptic release of serotonin (5-HT). Interactions between MDMA and 5-HT receptor antagonists suggest that the activating effects of MDMA are mediated via 5-HT1-like receptors. In order to assess the contribution of particular 5-HT receptor subtypes to the behavioral effects of MDMA, the present studies examined the development of tolerance and cross-tolerance to the behavioral effects of MDMA and selective 5-HT receptor agonists. In the first study, rats were pretreated with saline, a 5-HT1A receptor agonist (8-hydroxy-2-(di-n-propylamino)tetralin, 1.0 mg/kg), a 5-HT1B receptor agonist [5-methoyx-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole butane dioate (RU24969), 2.5 mg/kg] or a 5-HT1C/5-HT2 receptor agonist (2,5-dimethoxy-4-iodoamphetamine, 1.0 mg/kg) twice daily for 3 days. The behavioral response to S-MDMA (3.0 mg/kg) was assessed 36 hr after the last pretreatment injection. Pretreatment with RU24969 antagonized the activating effects of S-MDMA. In contrast, pretreatment with 2,5-dimethoxy-4-iodoamphetamine did not alter the response to S-MDMA, and pretreatment with 8-hydroxy-2-(di-n-propylamino)tetralin reduced the activity of both control and S-MDMA-treated animals. In the second study, rats were pretreated with saline or RS-MDMA (10 mg/kg), twice daily for 4 days. The behavioral response to saline, S-MDMA (3.0 mg/kg), RU24969 (2.5 mg/kg) or S-amphetamine (1.0 mg/kg) was assessed 36 hr after the last pretreatment injection.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla.
C W
CW
Callaway
M A
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Geyer
D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004347:Drug Interactions; D004361:Drug Tolerance; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D051381:Rats; D017207:Rats, Sprague-Dawley; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D007211:Indoles; D017366:Serotonin Receptor Agonists; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole; D015104:3,4-Methylenedioxyamphetamine; D000661:Amphetamine; D018817:N-Methyl-3,4-methylenedioxyamphetamine