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.
Ball
Kevin T
KT
Department of Psychology and Program in Neural Science, Indiana University, 1101 East 10th Street, Bloomington, IN 47405, USA.
Rebec
George V
GV
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