Cocaine and amphetamine preferentially stimulate glutamate release in the limbic system: studies on the involvement of dopamine.
The effects of cocaine and d-amphetamine on extracellular glutamate and aspartate levels in the nucleus accumbens, prefrontal cortex, and striatum were studied by in vivo microdialysis in awake, freely moving rats. In the nucleus accumbens, glutamate levels were stimulated by cocaine (15-30 mg/kg, i.p.), GBR 12909 (15 mg/kg, i.p.), and d-amphetamine (2 mg/kg, i.p.), while aspartate levels were not affected. The increase in nucleus accumbens glutamate levels following cocaine (30 mg/kg) was calcium-dependent and was blocked by pretreatment with dopamine antagonists; haloperidol (0.2 mg/kg, i.p.), SCH 23390 (0.02 mg/kg, i.p.), and raclopride (1 mg/kg, i.p.), as well as local 6-OHDA lesions of the nucleus accumbens. In the prefrontal cortex, glutamate levels were stimulated by both cocaine (15-30 mg/kg, i.p.) and d-amphetamine (2 mg/kg, i.p.), while aspartate levels were moderately stimulated by d-amphetamine only. The increase in prefrontal cortex glutamate levels following cocaine (30 mg/kg) was calcium-dependent and was blocked by pretreatment with SCH 23390 (0.02 mg/kg, i.p.), but not haloperidol (0.2 mg/kg, i.p.) or raclopride (1 mg/kg, i.p.). In the striatum, glutamate and aspartate levels were not affected by either cocaine (15-30 mg/kg, i.p.) or d-amphetamine (2 mg/kg, i.p.). These findings demonstrate that stimulants enhance glutamate release in limbic brain structures, nucleus accumbens, and prefrontal cortex, but not extrapyamidal brain structures, striatum. Furthermore, the increase in glutamate release in the nucleus accumbens may be mediated by dopamine.
Reid
M S
MS
University of California, San Francisco, Langley Porter Psychiatric Institute, Veteran's Affairs Medical Center 94121, USA. msreid@itsa.ucsf.edu
Hsu
K
K
Berger
S P
SP
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003042:Cocaine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D008032:Limbic System / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D018698:Glutamic Acid; D000661:Amphetamine; D003042:Cocaine; D004298:Dopamine