Amphetamine derivatives induce locomotor hyperactivity by acting as indirect serotonin agonists.
C W Callaway, M P Johnson, L H Gold, D E Nichols, Mark A. Geyer
Psychopharmacology 1991 DOI: 10.1007/bf02246026 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | MBDB fluoxetine S-(+)MDMA p-chloroamphetamine |
| Dose | 1.25, 2.5, 5.0 or 10.0 mg/kg MBDB; 2.5 or 10 mg/kg fluoxetine; 3.0 mg/kg S-(+)MDA; 2.5 mg/kg p-chloroamphetamine; 3.0 mg/kg S-(+)MDMA |
| Duration | 40 minutes after administration for tissue level measurements; hyperactivity lasted greater than 60 minutes after 5.0 and 10.0 mg/kg doses |
| Topics | Serotonin |
| Citations | 70 |
| Key findings | MBDB induces locomotor hyperactivity through serotonin release, not dopamine release, as shown by blockade with fluoxetine. |
Abstract
Derivatives of amphetamine are potent releasers of both dopamine (DA) and serotonin (5-HT), but the relative contributions of DA and 5-HT release to the behavioral effects of these drugs have not been established. Previously, S-(+)3,4-methylenedioxymethamphetamine (S-(+)MDMA) was found to produce locomotor hyperactivity in rats which was dependent on 5-HT release. The present study found that MBDB (1.25, 2.5, 5.0 or 10.0 mg/kg), the alpha-ethyl derivative of MDMA that produces little or no direct DA release, also induced locomotor hyperactivity that lasted for greater than 60 min after the 5.0 and 10.0 mg/kg doses. MBDB produced spatial patterns of locomotor hyperactivity and suppression of exploratory activity (holepokes and rearings) very similar to the behavioral syndrome produced by MDMA. MBDB-induced hyperactivity was blocked by pretreatment with the selective 5-HT uptake inhibitor fluoxetine (2.5 or 10 mg/kg), suggesting that MBDB produced behavioral effects via uptake-carrier mediated release of 5-HT. Similarly, fluoxetine pretreatment blocked the locomotor hyperactivity produced by S-(+)3,4-methylenedioxyamphetamine (3.0 mg/kg) or p-chloroamphetamine (2.5 mg/kg), supporting a serotonergic basis for the action of these drugs. Tissue levels of 5-HT and its metabolite 5-HIAA were decreased 40 min after administration of S-(+)MDMA (3.0 mg/kg) or MBDB (5.0 mg/kg), and these decreases were prevented by fluoxetine pretreatment. S-(+)MDMA also produced a fluoxetine-sensitive increase of tissue DA levels, suggesting that 5-HT release may indirectly result in increased DA release, although MBDB did not significantly increase DA levels.(ABSTRACT TRUNCATED AT 250 WORDS)