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Reinforcing effects of certain serotonin-releasing amphetamine derivatives.
Pharmacol Biochem Behav. 1996 Jan; 53(1):99-105.PB

Abstract

The present study was designed to characterize further the rewarding and aversive properties of 3,4-methylenedioxymethamphetamine (MDMA), the alpha-ethyl homologue of MDMA (MBDB), fenfluramine, and the selective serotonin releasing agent 5-methoxy-6-methyl-2-aminoindan (MMAI) using the conditioned place preference paradigm (CPP). Extracellular dopamine (DA) and its metabolite DOPAC were also measured in the nucleus accumbens after systemic drug administration, using in vivo microdialysis in freely moving rats. MDMA produced a positive dose-dependent effect in the CPP test, which was maximal at doses of 5 and 10 mg/kg. MBDB also induced a positive CPP, with a maximum effect at 10 mg/kg. The conditioning effect of MBDB was more than 2.5-fold weaker compared with MDMA. Fenfluramine evoked place aversion at doses of 4, 6, and 10 mg/kg. This effect of fenfluramine was independent of dose. MMAI at doses of 1.25, 2.5, and 5 mg/kg produced no significant effect on place conditioning. At doses of 10 and 20 mg/kg, MMAI produced an effect similar to fenfluramine: Place aversion was independent of dose. In the microdialysis experiments, MDMA significantly elevated extracellular DA and induced a decrease of DOPAC in the nucleus accumbens. Thus, activation of dopaminergic systems may be responsible for the rewarding properties of MDMA-like drugs. In contrast to the effects seen with MDMA, no difference in extracellular DA or DOPAC was seen after injection of MBDB, fenfluramine, or MMAI, even though MBDB weakly induced a place preference. The mechanism responsible for the development of place aversion by fenfluramine or MMAI is unknown at this time and requires further study.

Authors+Show Affiliations

Department of Pharmacology, Purdue University, West Lafayette, IN 47907, USA.No 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

8848466

Citation

Marona-Lewicka, D, et al. "Reinforcing Effects of Certain Serotonin-releasing Amphetamine Derivatives." Pharmacology, Biochemistry, and Behavior, vol. 53, no. 1, 1996, pp. 99-105.
Marona-Lewicka D, Rhee GS, Sprague JE, et al. Reinforcing effects of certain serotonin-releasing amphetamine derivatives. Pharmacol Biochem Behav. 1996;53(1):99-105.
Marona-Lewicka, D., Rhee, G. S., Sprague, J. E., & Nichols, D. E. (1996). Reinforcing effects of certain serotonin-releasing amphetamine derivatives. Pharmacology, Biochemistry, and Behavior, 53(1), 99-105.
Marona-Lewicka D, et al. Reinforcing Effects of Certain Serotonin-releasing Amphetamine Derivatives. Pharmacol Biochem Behav. 1996;53(1):99-105. PubMed PMID: 8848466.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reinforcing effects of certain serotonin-releasing amphetamine derivatives. AU - Marona-Lewicka,D, AU - Rhee,G S, AU - Sprague,J E, AU - Nichols,D E, PY - 1996/1/1/pubmed PY - 1996/1/1/medline PY - 1996/1/1/entrez SP - 99 EP - 105 JF - Pharmacology, biochemistry, and behavior JO - Pharmacol Biochem Behav VL - 53 IS - 1 N2 - The present study was designed to characterize further the rewarding and aversive properties of 3,4-methylenedioxymethamphetamine (MDMA), the alpha-ethyl homologue of MDMA (MBDB), fenfluramine, and the selective serotonin releasing agent 5-methoxy-6-methyl-2-aminoindan (MMAI) using the conditioned place preference paradigm (CPP). Extracellular dopamine (DA) and its metabolite DOPAC were also measured in the nucleus accumbens after systemic drug administration, using in vivo microdialysis in freely moving rats. MDMA produced a positive dose-dependent effect in the CPP test, which was maximal at doses of 5 and 10 mg/kg. MBDB also induced a positive CPP, with a maximum effect at 10 mg/kg. The conditioning effect of MBDB was more than 2.5-fold weaker compared with MDMA. Fenfluramine evoked place aversion at doses of 4, 6, and 10 mg/kg. This effect of fenfluramine was independent of dose. MMAI at doses of 1.25, 2.5, and 5 mg/kg produced no significant effect on place conditioning. At doses of 10 and 20 mg/kg, MMAI produced an effect similar to fenfluramine: Place aversion was independent of dose. In the microdialysis experiments, MDMA significantly elevated extracellular DA and induced a decrease of DOPAC in the nucleus accumbens. Thus, activation of dopaminergic systems may be responsible for the rewarding properties of MDMA-like drugs. In contrast to the effects seen with MDMA, no difference in extracellular DA or DOPAC was seen after injection of MBDB, fenfluramine, or MMAI, even though MBDB weakly induced a place preference. The mechanism responsible for the development of place aversion by fenfluramine or MMAI is unknown at this time and requires further study. SN - 0091-3057 UR - https://www.unboundmedicine.com/medline/citation/8848466/Reinforcing_effects_of_certain_serotonin_releasing_amphetamine_derivatives_ L2 - https://linkinghub.elsevier.com/retrieve/pii/0091-3057(95)00205-7 DB - PRIME DP - Unbound Medicine ER -