Regional neurochemical profile following development of apomorphine-induced reinforcement.
Dopamine is primary neurotransmitter which mediates the reinforcing effects of abused drugs, serotonin (5-Hydroxytryptamine; 5-HT) also has a crucial role in the pathophysiology of addiction. The binding sites of various drugs of abuse are different from each other, their final rewarding effects are mediated by an increase in the dopamine level in the Nucleus Accumbens. The present study used conditioned place preference (CPP) test to monitor apomorphine's reinforcing effects. Associated alterations in 5-HT and dopamine metabolism were also monitored in various brain regions by HPLC-EC. Withdrawal from apomorphine administration (at a dose of 1.0 mg/kg on six alternate days) induced reinforcement as monitored in the conditioned place preference (CPP) paradigm. Serotonin and dopamine metabolism was also changed particularly in the ventral and dorsal striatum. Results therefore suggest desensitization of dopamine receptors in the presynaptic site is involved in apomorphine-induced reinforcement. Desensitization of somatodendritic 5-HT(1A) receptors resulting in increased availability of 5-HT at 5-HT(2C) receptors could attenuate apomorphine-induced reinforcement. Therefore, further investigations in this area should focus on attempts to attenuate apomorphine-induced reinforcement by desensitizing somatodendritic 5-HT(1A) receptors.
Department of Biochemistry, University of Karachi, Karachi, Pakistan. huma_biochemist@yahoo.com
Huma
H
Ikram
Adnan Maqsood
AM
Choudhry
Darakhshan Jabeen
DJ
Haleem
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003213:Conditioning, Psychological / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects / Q000502:physiology; D044405:Receptor, Serotonin, 5-HT2C / Q000187:drug effects / Q000502:physiology; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology; D012054:Reinforcement, Psychology; D012701:Serotonin / Q000378:metabolism
D044405:Receptor, Serotonin, 5-HT2C; D011954:Receptors, Dopamine; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D001058:Apomorphine; D004298:Dopamine