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Amphetamine derivatives induce locomotor hyperactivity by acting as indirect serotonin agonists.
Psychopharmacology (Berl). 1991; 104(3):293-301.P

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)

Authors+Show Affiliations

Department of Psychiatry, University of California, San Diego, School of Medicine, La Jolla 92093-0804.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

1924637

Citation

Callaway, C W., et al. "Amphetamine Derivatives Induce Locomotor Hyperactivity By Acting as Indirect Serotonin Agonists." Psychopharmacology, vol. 104, no. 3, 1991, pp. 293-301.
Callaway CW, Johnson MP, Gold LH, et al. Amphetamine derivatives induce locomotor hyperactivity by acting as indirect serotonin agonists. Psychopharmacology (Berl). 1991;104(3):293-301.
Callaway, C. W., Johnson, M. P., Gold, L. H., Nichols, D. E., & Geyer, M. A. (1991). Amphetamine derivatives induce locomotor hyperactivity by acting as indirect serotonin agonists. Psychopharmacology, 104(3), 293-301.
Callaway CW, et al. Amphetamine Derivatives Induce Locomotor Hyperactivity By Acting as Indirect Serotonin Agonists. Psychopharmacology (Berl). 1991;104(3):293-301. PubMed PMID: 1924637.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Amphetamine derivatives induce locomotor hyperactivity by acting as indirect serotonin agonists. AU - Callaway,C W, AU - Johnson,M P, AU - Gold,L H, AU - Nichols,D E, AU - Geyer,M A, PY - 1991/1/1/pubmed PY - 1991/1/1/medline PY - 1991/1/1/entrez SP - 293 EP - 301 JF - Psychopharmacology JO - Psychopharmacology (Berl) VL - 104 IS - 3 N2 - 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) SN - 0033-3158 UR - https://www.unboundmedicine.com/medline/citation/1924637/Amphetamine_derivatives_induce_locomotor_hyperactivity_by_acting_as_indirect_serotonin_agonists_ DB - PRIME DP - Unbound Medicine ER -