Modulation of cortical acetylcholine and gamma-aminobutyric acid release in freely moving guinea pigs: effects of clonidine and other adrenergic drugs.
The effects of various doses of clonidine and norepinephrine (NE) on the release of acetylcholine (ACh) and gamma-aminobutyric acid (GABA) from the brain surface of freely moving guinea pigs have been investigated in order to study the role of alpha adrenoceptors on the function of cortical cholinergic and GABAergic neurons. Clonidine administration at doses of 7.5 and 18.7 nmol/kg inhibits by 40% the release of ACh; larger doses (112 nmol/kg) are inactive. On the other hand, the largest dose of clonidine used in this study (112 nmol/kg) increases the release of GABA by 45%, whereas lower doses are inactive. Norepinephrine (0.9 mumol i.c.v.) decreases by 40% the release of ACh and increases by 80% that of GABA. The inhibitory effects of clonidine and of NE on cortical ACh output are completely antagonized by yohimbine (0.28 mumol/kg), a selective alpha-2 antagonist, thus suggesting an involvement of the alpha-2 adrenoceptors in the neurochemical action of the drug. However, yohimbine releases GABA and does not prevent the action of clonidine or of NE on the cortical GABA system. On the other hand, prazosin (35.8 nmol/kg), a selective alpha-1 antagonist, completely antagonizes the stimulating effects of clonidine and of NE on the release of GABA, suggesting that alpha-1 receptors modulate this release. The present experiments indicate that the neurochemical and neuropharmacological profile of activity of clonidine is strictly dependent upon the dose of the drug. In addition, they support the concept that cortical alpha adrenoceptors modulate the function of neurons releasing ACh or GABA.
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003000:Clonidine / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D013566:Sympathomimetics / Q000494:pharmacology*; D015016:Yohimbine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D011942:Receptors, Adrenergic, alpha; D013566:Sympathomimetics; D015016:Yohimbine; D005680:gamma-Aminobutyric Acid; D003000:Clonidine; D000109:Acetylcholine; D009638:Norepinephrine; D011224:Prazosin