Systemic administration of baclofen and the GABAB antagonist, CGP 35348, does not affect GABA, glutamate or aspartate in microdialysates of the striatum of conscious rats.
Previous in vitro experiments have shown that the GABAB agonist, baclofen, and the antagonist, CGP 35348, respectively, decrease and increase the autoreceptor-mediated release of GABA in brain slices and synaptosomes. Since it is not clear whether these autoreceptors are operative in vivo, an attempt was made to reproduce these results in brain dialysis experiments, knowing that only positive results would permit a conclusion in view of the doubts expressed in the literature with respect to the origin of extracellular GABA. Because of older reports of an inhibitory action of baclofen on the in vitro release of glutamate, which might be ascribed to the action of presynaptic GABAB heteroreceptors, extracellular glutamate and aspartate were also measured. Neither (-)-baclofen, administered systemically at a dose of 20 mg/kg i.p., nor the GABAB antagonist, CGP 35348 (300 mg/kg i.p.) had significant effects on basal overflow of GABA, glutamate, or aspartate nor on that evoked by 100 mmol/l K+ in the striatum of the conscious, freely moving rat. To ascertain this result, (-)-baclofen was also administered between two K+ stimulations, so that the first stimulation could serve as an intraindividual control of the second. The compound did not significantly affect K+ evoked overflow of any of the three transmitter amino acids under these conditions. It must be emphasized that these data do not exclude the operativity of presynaptic GABAB auto- and heteroreceptors in vivo. They only suggest that this question must, in all probability, be addressed by other techniques than brain dialysis.
Research Department, Ciba-Geigy AG, Basel, Switzerland.
P C
PC
Waldmeier
K
K
Stöcklin
J J
JJ
Feldtrauer
D000818:Animals; D001224:Aspartic Acid / Q000008:administration & dosage / Q000032:analysis*; D001418:Baclofen / Q000008:administration & dosage / Q000494:pharmacology*; D003342:Corpus Striatum / Q000737:chemistry* / Q000187:drug effects; D003956:Dialysis; D058787:GABA-A Receptor Antagonists; D005971:Glutamates / Q000008:administration & dosage / Q000032:analysis*; D018698:Glutamic Acid; D008297:Male; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000032:analysis*
D058787:GABA-A Receptor Antagonists; D005971:Glutamates; D009943:Organophosphorus Compounds; D001224:Aspartic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C066430:CGP 35348; D001418:Baclofen; D011188:Potassium