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.
BACKGROUND
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.


OBJECTIVE
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.


CONCLUSIONS
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.
Department of Psychology and Program in Neural Science, Indiana University, 1101 East 10th Street, Bloomington, IN 47405, USA.
Kevin T
KT
Ball
George V
GV
Rebec
D019969:Amphetamine-Related Disorders / Q000503:physiopathology; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism; D004569:Electroencephalography / Q000187:drug effects*; D005464:Fluorobenzenes / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects; D010636:Phenols / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects*; D044403:Receptor, Serotonin, 5-HT2B / Q000187:drug effects*; D044405:Receptor, Serotonin, 5-HT2C / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D005464:Fluorobenzenes; D007211:Indoles; D010636:Phenols; D011725:Pyridines; D044402:Receptor, Serotonin, 5-HT2A; D044403:Receptor, Serotonin, 5-HT2B; D044405:Receptor, Serotonin, 5-HT2C; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C076033:SR 46349B; C094868:SB 206553; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine