Potential roles of GABA receptors in morphine self-administration in rats.
It is well established that the reinforcing effect of drugs of abuse is linked to the mesolimbic dopamine (DA) system. Morphine produces an increase in DA release in the brain, which may provide positive reinforcement contributing to the development of motivational aspects of drug-seeking and maintenance behavior. Several studies suggest that the GABA receptor system may play a significant role in the modulating the mesolimbic DA system. The purpose of this study was to investigate potential roles for GABA agonists in morphine self-administration behavior. Male Sprague-Dawley rats were trained to self-administrated morphine (0.1 mg/kg per injection) during daily 1-h sessions under a fixed ratio 1 schedule. Rats received an intravenous injection of the selective GABA(B) antagonist SCH 50911 (2.0 mg/kg) or an intraperitoneal injection of the GABA(A) antagonist bicuculline (1.0 mg/kg), immediately followed by either an intraperitoneal injection of baclofen (1.25 or 1.8 mg/kg) or muscimol (0.5 or 1.0 mg/kg, i.p.), 30 min prior to the start of test session. Results showed that pretreatment with baclofen or muscimol reduced morphine-maintenance response in a dose-dependent fashion and that baclofen and muscimol effects were reversed by injections of SCH 50911 and bicuculline, respectively. These data suggest that activation of both GABA(A) and GABA(B) receptors may be effective in suppressing the reinforcing effects of morphine.
Yoon
Seong Shoon
SS
College of Pharmacy, Yeungnam University, Gyeongsan, South Korea.
Lee
Bong Hyo
BH
Kim
Hey Soo
HS
Choi
Ki Hwan
KH
Yun
Jaesuk
J
Jang
Eun Young
EY
Shim
Insop
I
Kim
Jung-Ae
JA
Kim
Mi Ryeo
MR
Yang
Chae Ha
CH
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001640:Bicuculline / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D009025:Morpholines / Q000494:pharmacology; D009118:Muscimol / Q000494:pharmacology; D009294:Narcotics / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000502:physiology*; D012054:Reinforcement, Psychology; D012646:Self Administration
C095804:(+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid; D018755:GABA Agonists; D018756:GABA Antagonists; D009025:Morpholines; D009294:Narcotics; D018079:Receptors, GABA; D009118:Muscimol; D009020:Morphine; D001640:Bicuculline