Serotonergic properties of cocaine: effects on a 5-HT2 receptor-mediated behavior and on extracellular concentrations of serotonin and dopamine.
The present study examined the ability of cocaine to produce behavioral and neuropharmacological effects through serotonin (5-HT) systems. Pretreatment with fluoxetine or cocaine potentiated the head-shake response to the 5-HT precursor, 5-hydroxytryptophan (5-HTP; 75 mg/kg), a behavior mediated by the activation of 5-HT2 receptors. This effect was antagonized by the selective 5-HT2 receptor antagonist ketanserin (1 mg/kg). In contrast, pretreatment with the selective norepinephrine uptake inhibitor desipramine (10 mg/kg) or the selective dopamine (DA) uptake inhibitor GBR 12909 (32 mg/kg) failed to potentiate the head-shake response. The effects of cocaine on extracellular concentrations of DA and 5-HT in the nucleus accumbens were examined using in vivo microdialysis in a separate group of anesthetized rats. Cocaine (10 mg/kg) increased the extracellular concentrations of DA and 5-HT by 300-350% over baseline levels. Cocaine's ability to increase the head-shake response and to increase extracellular concentrations of 5-HT may be due to its ability to block 5-HT uptake.
Essman
W D
WD
Department of Psychiatry, University of Pennsylvania, Philadelphia 19104-2649.
Singh
A
A
Lucki
I
I
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D003042:Cocaine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004563:Electrochemistry; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects
D018765:Dopamine Uptake Inhibitors; D010879:Piperazines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D012701:Serotonin; C043425:vanoxerine; D007650:Ketanserin; D006916:5-Hydroxytryptophan; D003042:Cocaine; D004298:Dopamine