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Role of 5-HT2A and 5-HT2C/B receptors in the acute effects of 3,4-methylenedioxymethamphetamine (MDMA) on striatal single-unit activity and locomotion in freely moving rats.
Psychopharmacology (Berl). 2005 Oct; 181(4):676-87.P

Abstract

RATIONALE

Like amphetamine, a locomotor-activating dose of 3,4-methylenedioxymethamphetamine (MDMA) predominantly excites striatal single-unit activity in freely moving rats. Although both D1- and D2-like dopamine (DA) receptors play important roles in this effect, MDMA, unlike amphetamine, strongly increases both DA and serotonin (5-HT) transmission.

OBJECTIVES

This study was conducted to investigate the 5-HT receptor mechanisms underlying the striatal effects of MDMA.

METHODS

We recorded the activity of >200 single units in the striatum of awake, unrestrained rats in response to acute MDMA administration (5 mg/kg) combined with the selective blockade of either 5-HT2A or 5-HT2C/B receptors.

RESULTS

Prior administration of SR-46349B (a 5-HT2A antagonist 0.5 mg/kg) blocked nearly all MDMA-induced striatal excitations, which paralleled its significant attenuation of MDMA-induced locomotor activation. Conversely, prior administration of SB-206553 (a 5-HT2C/B antagonist 2.0 mg/kg) had no effect on the amount of MDMA-induced locomotor activation or the distribution of single-unit responses to MDMA. However, a coefficient-of-variation analysis indicated significantly less variability in the magnitude of both MDMA-induced neuronal excitations and inhibitions in rats that were pretreated with SB-206553 compared to vehicle. Analysis of concurrent single-unit activity and behavior confirmed that MDMA-induced striatal activation was not merely due to behavioral feedback, indicating a primary action of MDMA.

CONCLUSION

These results support and extend our previous findings by showing that 5-HT2A and 5-HT2C/B receptors differentially regulate the expression of MDMA-induced behavioral and striatal neuronal responses, either directly or through the modulation of DA transmission.

Authors+Show Affiliations

Department of Psychology and Program in Neural Science, Indiana University, 1101 East 10th Street, Bloomington, IN 47405, USA.No affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

16001122

Citation

Ball, Kevin T., and George V. Rebec. "Role of 5-HT2A and 5-HT2C/B Receptors in the Acute Effects of 3,4-methylenedioxymethamphetamine (MDMA) On Striatal Single-unit Activity and Locomotion in Freely Moving Rats." Psychopharmacology, vol. 181, no. 4, 2005, pp. 676-87.
Ball KT, Rebec GV. Role of 5-HT2A and 5-HT2C/B receptors in the acute effects of 3,4-methylenedioxymethamphetamine (MDMA) on striatal single-unit activity and locomotion in freely moving rats. Psychopharmacology (Berl). 2005;181(4):676-87.
Ball, K. T., & Rebec, G. V. (2005). Role of 5-HT2A and 5-HT2C/B receptors in the acute effects of 3,4-methylenedioxymethamphetamine (MDMA) on striatal single-unit activity and locomotion in freely moving rats. Psychopharmacology, 181(4), 676-87.
Ball KT, Rebec GV. Role of 5-HT2A and 5-HT2C/B Receptors in the Acute Effects of 3,4-methylenedioxymethamphetamine (MDMA) On Striatal Single-unit Activity and Locomotion in Freely Moving Rats. Psychopharmacology (Berl). 2005;181(4):676-87. PubMed PMID: 16001122.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of 5-HT2A and 5-HT2C/B receptors in the acute effects of 3,4-methylenedioxymethamphetamine (MDMA) on striatal single-unit activity and locomotion in freely moving rats. AU - Ball,Kevin T, AU - Rebec,George V, Y1 - 2005/09/29/ PY - 2004/09/23/received PY - 2005/04/19/accepted PY - 2005/7/8/pubmed PY - 2006/3/3/medline PY - 2005/7/8/entrez SP - 676 EP - 87 JF - Psychopharmacology JO - Psychopharmacology (Berl) VL - 181 IS - 4 N2 - RATIONALE: Like amphetamine, a locomotor-activating dose of 3,4-methylenedioxymethamphetamine (MDMA) predominantly excites striatal single-unit activity in freely moving rats. Although both D1- and D2-like dopamine (DA) receptors play important roles in this effect, MDMA, unlike amphetamine, strongly increases both DA and serotonin (5-HT) transmission. OBJECTIVES: This study was conducted to investigate the 5-HT receptor mechanisms underlying the striatal effects of MDMA. METHODS: We recorded the activity of >200 single units in the striatum of awake, unrestrained rats in response to acute MDMA administration (5 mg/kg) combined with the selective blockade of either 5-HT2A or 5-HT2C/B receptors. RESULTS: Prior administration of SR-46349B (a 5-HT2A antagonist 0.5 mg/kg) blocked nearly all MDMA-induced striatal excitations, which paralleled its significant attenuation of MDMA-induced locomotor activation. Conversely, prior administration of SB-206553 (a 5-HT2C/B antagonist 2.0 mg/kg) had no effect on the amount of MDMA-induced locomotor activation or the distribution of single-unit responses to MDMA. However, a coefficient-of-variation analysis indicated significantly less variability in the magnitude of both MDMA-induced neuronal excitations and inhibitions in rats that were pretreated with SB-206553 compared to vehicle. Analysis of concurrent single-unit activity and behavior confirmed that MDMA-induced striatal activation was not merely due to behavioral feedback, indicating a primary action of MDMA. CONCLUSION: These results support and extend our previous findings by showing that 5-HT2A and 5-HT2C/B receptors differentially regulate the expression of MDMA-induced behavioral and striatal neuronal responses, either directly or through the modulation of DA transmission. SN - 0033-3158 UR - https://www.unboundmedicine.com/medline/citation/16001122/Role_of_5_HT2A_and_5_HT2C/B_receptors_in_the_acute_effects_of_34_methylenedioxymethamphetamine__MDMA__on_striatal_single_unit_activity_and_locomotion_in_freely_moving_rats_ L2 - https://dx.doi.org/10.1007/s00213-005-0038-z DB - PRIME DP - Unbound Medicine ER -