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GABAergic and glycinergic mechanisms within the substantia nigra: Pharmacological specificity of dopamine-independent contralateral turning behavior and interactions with other neurotransmitters

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Abstract

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 α-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.

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Authors and Affiliations

  1. Department of Pharmacology, Royal Danish School of Pharmacy, 2 Universitetsparken, DK-2100, Copenhagen Ø, Denmark

    Jørn Arnt

  2. Psychopharmacological Research Laboratory, Department E, Sct. Hans Mental Hospital, Roskilde, Denmark

    Jørgen Scheel-Krüger

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  1. Jørn Arnt
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Arnt, J., Scheel-Krüger, J. GABAergic and glycinergic mechanisms within the substantia nigra: Pharmacological specificity of dopamine-independent contralateral turning behavior and interactions with other neurotransmitters. Psychopharmacology 62, 267–277 (1979). https://doi.org/10.1007/BF00431958

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