GABAergic and glycinergic mechanisms within the substantia nigra: pharmacological specificity of dopamine-independent contralateral turning behavior and interactions with other neurotransmitters.
The pharmacological specificity of the GABA agonist muscimol-induced contralateral turning behavior after unilateral injection into substantia nigra pars reticulata (SNR) has been studied. Muscimol-induced turning was antagonized by intranigral bicuculline methochloride (BMC) and picrotoxin, whereas antagonists of glycine, morphine, dopamine, noradrenaline, and serotonin were ineffective. Glycine induced a qualitatively similar turning behavior which was strychnine-sensitive but relatively BMC and picrotoxin-insensitive. Other drugs, including substance P, kainic acid, clonidine, oxymetazoline, serotonin, and carbachol, induced turning that could be dissociated from the effect of muscimol. Muscimol-induced turning was dopamine-independent, indicated by resistance to haloperidol (1 mg/kg), to pretreatment with reserpine (7.5 mg/kg) plus alpha-methyl-p-tyrosine (200 mg/kg), to haloperidol injections into the SNR, striatum and nucleus accumbens, and finally to kainic acid lesions of the striatum. 6-Hydroxydopamine lesions increased the efficacy of intranigral muscimol, while kainic acid lesions of the SNR antagonized muscimol. Muscimol-induced turning was inhibited by oxotremorine (0.25 mg/kg), by intranigral carbachol, and by apomorphine (0.1--0.5 mg/kg), but only moderately by intranigrally injected apomorphine. These data suggest specificity of GABA-agonist-induced contralateral turning and indicate an interaction between nigral GABA and other neurotransmitters, particularly dopamine and acetylcholine.
D000818:Animals; D001519:Behavior / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D005998:Glycine / Q000502:physiology*; D006801:Humans; D006892:Hydroxydopamines / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000502:physiology*; D051381:Rats; D013239:Stereotyped Behavior / Q000187:drug effects*; D013378:Substantia Nigra / Q000033:anatomy & histology / Q000502:physiology*; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D006892:Hydroxydopamines; D018377:Neurotransmitter Agents; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D007608:Kainic Acid; D005998:Glycine; D004298:Dopamine