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Multiple 5-HT receptors are involved in the effects of acute MDMA treatment: studies on locomotor activity and responding for conditioned reinforcement.
Psychopharmacology (Berl). 2002 Jul; 162(3):282-91.P

Abstract

RATIONALE

Responding for conditioned reinforcement is increased by the dopamine releasing agent amphetamine, but reduced by drugs that enhance serotonin (5-HT) function. The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) releases both monoamines.

OBJECTIVES

The primary purpose of this study was to examine the effects of MDMA on responding for conditioned reinforcement as well as on locomotor activity. The roles of several 5-HT receptor sub-types in mediating these behavioural effects of MDMA were also examined.

METHODS

Locomotion was measured in photocell activity monitors. For conditioned reinforcement experiments thirsty rats learned to associate a conditioned stimulus (CS) with water in operant chambers. Subsequently, two response levers were available; responding on one lever delivered the CS, while responding on the second lever had no consequences. Drug effects on this operant response were measured.

RESULTS

MDMA dose-dependently increased locomotion but reduced responding for conditioned reinforcement. This latter effect differs from that induced by amphetamine, which potentiates conditioned reinforcement responding. The stimulant effect of MDMA was attenuated by GR127935 and ketanserin, indicating facilitatory roles of 5-HT(1B) and 5-HT(2A) receptors in mediating this effect. The 5-HT(2C) antagonist SB242084 enhanced the stimulant effect of MDMA. Only SB242084 attenuated the suppressant effect of MDMA on responding for conditioned reinforcement.

CONCLUSIONS

The results show that 5-HT(2A) and 5-HT(1B/1D) receptors play a facilitatory role in mediating the stimulant effect of MDMA, whereas 5-HT(2C) receptors are inhibitory. Activation of 5-HT(2C) receptors also contributes to the deficit in operant responding. Multiple 5-HT receptor sub-types appear to contribute to the behavioural effects of MDMA.

Authors+Show Affiliations

Section of Biopsychology, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, Canada, M5T 1R8. Paul_Fletcher@camh.netNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12122486

Citation

Fletcher, Paul J., et al. "Multiple 5-HT Receptors Are Involved in the Effects of Acute MDMA Treatment: Studies On Locomotor Activity and Responding for Conditioned Reinforcement." Psychopharmacology, vol. 162, no. 3, 2002, pp. 282-91.
Fletcher PJ, Korth KM, Robinson SR, et al. Multiple 5-HT receptors are involved in the effects of acute MDMA treatment: studies on locomotor activity and responding for conditioned reinforcement. Psychopharmacology (Berl). 2002;162(3):282-91.
Fletcher, P. J., Korth, K. M., Robinson, S. R., & Baker, G. B. (2002). Multiple 5-HT receptors are involved in the effects of acute MDMA treatment: studies on locomotor activity and responding for conditioned reinforcement. Psychopharmacology, 162(3), 282-91.
Fletcher PJ, et al. Multiple 5-HT Receptors Are Involved in the Effects of Acute MDMA Treatment: Studies On Locomotor Activity and Responding for Conditioned Reinforcement. Psychopharmacology (Berl). 2002;162(3):282-91. PubMed PMID: 12122486.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Multiple 5-HT receptors are involved in the effects of acute MDMA treatment: studies on locomotor activity and responding for conditioned reinforcement. AU - Fletcher,Paul J, AU - Korth,Karin M, AU - Robinson,Shannon R, AU - Baker,Glen B, Y1 - 2002/05/14/ PY - 2001/11/01/received PY - 2002/03/08/accepted PY - 2002/7/18/pubmed PY - 2003/2/27/medline PY - 2002/7/18/entrez SP - 282 EP - 91 JF - Psychopharmacology JO - Psychopharmacology (Berl.) VL - 162 IS - 3 N2 - RATIONALE: Responding for conditioned reinforcement is increased by the dopamine releasing agent amphetamine, but reduced by drugs that enhance serotonin (5-HT) function. The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) releases both monoamines. OBJECTIVES: The primary purpose of this study was to examine the effects of MDMA on responding for conditioned reinforcement as well as on locomotor activity. The roles of several 5-HT receptor sub-types in mediating these behavioural effects of MDMA were also examined. METHODS: Locomotion was measured in photocell activity monitors. For conditioned reinforcement experiments thirsty rats learned to associate a conditioned stimulus (CS) with water in operant chambers. Subsequently, two response levers were available; responding on one lever delivered the CS, while responding on the second lever had no consequences. Drug effects on this operant response were measured. RESULTS: MDMA dose-dependently increased locomotion but reduced responding for conditioned reinforcement. This latter effect differs from that induced by amphetamine, which potentiates conditioned reinforcement responding. The stimulant effect of MDMA was attenuated by GR127935 and ketanserin, indicating facilitatory roles of 5-HT(1B) and 5-HT(2A) receptors in mediating this effect. The 5-HT(2C) antagonist SB242084 enhanced the stimulant effect of MDMA. Only SB242084 attenuated the suppressant effect of MDMA on responding for conditioned reinforcement. CONCLUSIONS: The results show that 5-HT(2A) and 5-HT(1B/1D) receptors play a facilitatory role in mediating the stimulant effect of MDMA, whereas 5-HT(2C) receptors are inhibitory. Activation of 5-HT(2C) receptors also contributes to the deficit in operant responding. Multiple 5-HT receptor sub-types appear to contribute to the behavioural effects of MDMA. SN - 0033-3158 UR - https://www.unboundmedicine.com/medline/citation/12122486/Multiple_5_HT_receptors_are_involved_in_the_effects_of_acute_MDMA_treatment:_studies_on_locomotor_activity_and_responding_for_conditioned_reinforcement_ L2 - https://dx.doi.org/10.1007/s00213-002-1104-4 DB - PRIME DP - Unbound Medicine ER -