Alterations in extracellular and tissue levels of biogenic amines in rat brain induced by the serotonin2 receptor antagonist, ritanserin.
Systemic administration of ritanserin elicited rapid changes in dopamine (DA) and serotonin (5-HT) levels in both dialysate and neuronal tissue extracts. These effects occurred in both a site-selective and a dose-related manner. Increases in extracellular levels of DA and 5-HT in the nucleus accumbens were maximal at 120-140 min after treatment. A dose of 0.63 mg/kg of ritanserin elicited larger and more prolonged increases in extracellular DA and 5-HT levels than did the 0.3 mg/kg dose. By contrast, 0.63 mg/kg of ritanserin elicited no changes in either DA or 5-HT levels with dialysate collected from the striatum. Ritanserin also induced dose-related decreases in tissue levels of DA and 5-HT from the nucleus accumbens. The site specificity of action was again noted in that there were no dose-dependent decreases in tissue levels of DA or 5-HT measured from the striatum. Ritanserin exerted little effect on metabolite levels from either dialysate or tissue extracts. Taken together, these findings show that selective 5-HT2 receptor antagonism modulates DA and 5-HT neurotransmission in a specific manner. These actions appear to involve increased release of DA and 5-HT rather than significant changes in metabolism. These findings add further weight to the importance of 5-HT2 receptor interactions as an important component of antipsychotic activity.
Devaud
L L
LL
Division of Pharmacology, Wellcome Research Laboratories, Research Triangle Park, North Carolina.
Hollingsworth
E B
EB
Cooper
B R
BR
D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000378:metabolism*; D008297:Male; D009714:Nucleus Accumbens / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016713:Ritanserin / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists; D013997:Time Factors
D001679:Biogenic Amines; D012702:Serotonin Antagonists; D016713:Ritanserin; D012701:Serotonin; D004298:Dopamine