Serotonin 5-HT2C agonists selectively inhibit morphine-induced dopamine efflux in the nucleus accumbens.
In vivo microdialysis was used to compare the effects of serotonergic drugs on morphine- and cocaine-induced increases in extracellular dopamine (DA) concentrations in the rat nucleus accumbens (NAc). Systemic administration of the 5-HT2A/2C agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (2.5 mg/kg, s.c. ) prevented the increase in extracellular DA in the NAc produced by morphine (5 mg/kg, i.p.). In contrast, this dose of DOI had no effect on the ability of cocaine (10 mg/kg, i.p.) to increase extracellular DA concentrations in the NAc. A 5-HT2C selective agonist, 6-chloro-2-[1-piperazinyl]-pyrazine (MK-212, 5 mg/kg, s.c.) also inhibited morphine-induced increases in extracellular DA concentrations in the NAc. Pretreatment of rats with the selective 5-HT2A antagonist, amperozide, had no effect on morphine-induced elevation of NAc DA concentrations. In order to determine if inhibition of the firing of 5-HT neurons contributes to the serotonin agonist-mediated inhibition of morphine-induced accumbens DA release, rats were pretreated with the 5-HT1A agonist, 8-OHDPAT. At a dose of 100 microg/kg (sc), 8-OHDPAT did not interfere with morphine's ability to increase DA concentrations in the NAc. These results suggest that the activation of 5-HT2C receptors selectively inhibits morphine-induced DA release in the NAc in a manner which is independent of the inhibition of 5-HT neurons.
Willins
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DL
Department of Psychiatry, Case Western Reserve University, School of Medicine, Cleveland, OH 44106, USA. dwill63@aol.com
Meltzer
H Y
HY
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D009020:Morphine / Q000037:antagonists & inhibitors*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D011719:Pyrazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D000662:Amphetamines; D018765:Dopamine Uptake Inhibitors; D009292:Narcotic Antagonists; D010879:Piperazines; D011719:Pyrazines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C049058:amperozide; C014896:6-chloro-2-(1-piperazinyl)pyrazine; D009020:Morphine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D003042:Cocaine; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; D004298:Dopamine