Differential modulation of striatal dopamine release by intranigral injection of gamma-aminobutyric acid (GABA), dynorphin A and substance P.
The effects of intranigral injection of gamma-aminobutyric acid (GABA) (dose range: 10.0-300.0 nmol), dynorphin A (0.005-0.5 nmol) and substance P (0.00007-7.0 nmol) on striatal dopamine (DA) release, and dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) formation were studied by microdialysis. It was found that both GABA and dynorphin A produced a dose-dependent decrease in the release of striatal DA following injection into the ipsilateral substantia nigra, the pars reticulata. In contrast, intranigral injection of substance P produced an increase in DA release. However, the dose-response curve for the substance P effect had a biphasic shape. The maximum effect was produced by 0.007 nmol, whereas higher doses (0.07-0.7 nmol) produced less pronounced effects. At the highest dose (7.0 nmol), substance P produced a strong decrease of DA release. Striatal levels of DOPAC and HVA were enhanced by GABA, dynorphin A and substance P. The present results support the concept that substance P, directly or indirectly, provides a positive feed-back regulation for the release of striatal DA, whereas GABA and dynorphin exert a negative feed-back regulation.
Reid
M
M
Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Herrera-Marschitz
M
M
Hökfelt
T
T
Terenius
L
L
Ungerstedt
U
U
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004399:Dynorphins / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013373:Substance P / Q000008:administration & dosage / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000494:pharmacology*
D015102:3,4-Dihydroxyphenylacetic Acid; D013373:Substance P; D005680:gamma-Aminobutyric Acid; D004399:Dynorphins; D004298:Dopamine; D006719:Homovanillic Acid