Tolerance and cross-tolerance to the activating effects of 3,4-methylenedioxymethamphetamine and a 5-hydroxytryptamine1B agonist.
Journal of Pharmacology and Experimental Therapeutics October 1, 1992 DOI: 10.1016/s0022-3565(25)10342-x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study in rats Peer reviewed |
|---|---|
| Population | Rats (Sprague-Dawley implied by field context) |
| Interventions | S-MDMA RS-MDMA RU24969 2 S-amphetamine |
| Dose | S-MDMA 3.0 mg/kg; 8-OH-DPAT 1.0 mg/kg; RU24969 2.5 mg/kg; DOI 1.0 mg/kg; RS-MDMA 10 mg/kg; S-amphetamine 1.0 mg/kg |
| Duration | 3-day pretreatment (twice daily) with behavioral testing 36 hr after the last injection; second study used 4-day pretreatment (twice daily) with testing 36 hr after the last injection |
| Topics | MDMA |
| Keywords | Brain Animals Rats, sprague-dawley N-methyl-3,4-methylenedioxyamphetamine Indoles Behavior, animal Drug interactions Drug tolerance Male Serotonin receptor agonists |
| Key findings | Pretreatment with the 5-HT1B receptor agonist RU24969 antagonized S-MDMA-induced locomotor hyperactivity, whereas the 5-HT1C/5-HT2 agonist DOI did not alter the response and the 5-HT1A agonist 8-OH-DPAT reduced activity in both control and MDMA-treated animals. The authors interpret these results as suggesting that 5-HT1B receptors contribute to MDMA's activating effects. |
Abstract
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)
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
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