EFFECT OF ACUTE AND SUBCHRONIC NICOTINE TREATMENT ON CORTICAL EFFLUX OF [H-3] D-ASPARTATE AND ENDOGENOUS GABA IN FREELY MOVING GUINEA-PIGS

1 The [H-3]-D-aspartate preloading of the parietal cortex of freely moving guinea-pigs equipped with epidural cups makes it possible to investigate drug effects on the efflux of this radiolabel, assumed as a marker of the glutamatergic structures underlying the cup. In the same model, the efflux of [H-3]-gamma-aminobutyric acid ([H-3]-GABA) and endogenous GABA can be measured. 2 Nicotine, 0.9-3.6 mg kg-1, s.c., or 3-5-mu-g, i.c.v., increased the efflux of [H-3]-D-aspartate but reduced that of GABA. 3 These effects were mediated through mecamylamine-sensitive receptors but the ganglionic blocking agent was devoid of any primary activity. 4 The inhibition of GABA efflux induced by nicotine 3.6 mg kg-1, s.c., was abolished by methysergide 2 mg kg-1, i.p. and was reduced by naloxone 3 mg kg-1, i.p. pretreatment, suggesting the involvement of tryptaminergic and opioid systems. In contrast, muscarinic and catecholamine antagonists were ineffective. 5 Chronic treatment with nicotine (3.6 mg kg-1, twice daily for 16 days) reduced the facilitatory effect of [H-3]-D-aspartate and abolished the inhibition of endogenous GABA efflux. 6 A slight increase in the number of nicotinic binding sites (by use of [H-3]-nicotine as ligand) was found in the neocortex of chronically treated guinea-pigs. 7 The higher degree of tolerance to chronic nicotine treatment shown by GABA as compared with [H-3]-D-aspartate efflux suggests that adaptative changes of the inhibitory neuronal pools prevail. This may contribute to the reinforcing and addictive properties of nicotine.