Stimulation of GABA release from the rat neostriatum and globus pallidus in vivo by corticotropin-releasing factor.
This study conducted in vivo examined the changes in gamma-aminobutyric acid (GABA) release in push-pull perfusates of the caudate nucleus (CN) and the globus pallidus (GP) in response to corticotropin releasing factor (CRF). In the CN, CRF (10(-12), 10(-10), 10(-8) M) stimulated GABA release in a dose-related manner, the highest dose (10(-8) M) also potentiating the 25 mM K+-evoked response. The release of GABA in response to CRF (10(-8) M) was completely blocked by alpha-helical CRF9-41 (10(-6) M) which also attenuated the K+-evoked response to control K+-stimulated levels. In the GP, only the highest dose of CRF (10(-8) M) significantly stimulated GABA release, this dose also potentiating the K+-evoked release. Both responses were attenuated by the CRF receptor antagonist (10(-6) M). These results thus demonstrate that CRF can exert potent effects on GABA release within the rat neostriatum-pallidum by increasing the membrane excitability of GABA neurons/terminals and that such effects are mediated via receptors present on both the cell bodies/terminals of GABA-containing neurones. These effects of CRF suggest that the peptide may be an integral component of the neurochemical circuitry in the basal ganglia with relevance to the regulation of motor behaviour.
Sirinathsinghji
D J
DJ
Department of Neuroendocrinology, AFRC Institute of Animal Physiology and Genetics Research, Babraham, Cambridge, U.K.
Heavens
R P
RP
D000818:Animals; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005917:Globus Pallidus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D005680:gamma-Aminobutyric Acid; D003346:Corticotropin-Releasing Hormone; D011188:Potassium