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Behavioral differences induced by muscimol selectively injected into pars compacta and pars reticulata of Substantia Nigra
Authors:J Arnt  J Scheel-Krüger
Institution:(1) Department of Pharmacology, The Royal Danish School of Pharmacy, 2 Universitetsparken, DK-2100 Copenhagen Ø, Denmark;(2) Psychopharmacological Research Laboratory, Sct. Hans Mental Hospital, Dept. E, DK-4000 Roskilde, Denmark;(3) Present address: Department of Pharmacology and Toxicology, H. Lundbeck & Co A/S 7-9 Otiliavej, DK-2500 Copenhagen Valby
Abstract:Summary Turning behavior was recorded after injection of the GABA agonist muscimol into the caudal part of rat substantia nigra, pars compacta (SNC) or pars reticulata (SNR). Unilateral injection of muscimol (10–25 ng) into SNC induced ipsilateral body posture. Additional treatment with apomorphine (0.5 mg/kg, s.c.) produced intense ipsilateral turning. This effect was abolished in rats depleted of catecholamines by the combined treatment with reserpine plus agr-methyltyrosine. The ipsilateral turning was probably not mediated via inhibition of dopaminergic (DA) activity since unilateral SNC injections of the DA agonist apomorphine (2.5–10 mgrg) in contrast produced contralateral turning upon systemic apomorphine administration.Unilateral injection of muscimol into SNR induced strong contralateral turning, resistant to DA receptor blockade. In contrast, the contralateral turning was dose dependently antagonized by apomorphine (0.1–5 mg/kg, s.c.). Locally applied apomorphine (2.5–20 mgrg) into SNR, striatum or nucleus accumbens also antagonized intranigral muscimol, corpus striatum being the most sensitive area. Bilateral intrastriatal apomorphine was most effective, followed by unilateral injection into the ipsilateral striatum. The apomorphine antagonism was attenuated by additional haloperidol treatment, possibly indicating DA-specificity. Systemic amphetamine (2 mg/kg, i.p.) or local injection of the DA agonist ADTN (10–20 mgrg) into SNR, striatum or nucleus accumbens was without inhibitory effect on intranigral muscimol. These results suggest that the interaction between DA and nigral GABA is extremely complex: 1. Differential functional effects of a GABA agonist are found within SNC and SNR; 2. The turning behavior induced by muscimol injected into SNR is antagonized by stimulation of apomorphine sensitive DA receptors but not by those activated by amphetamine or ADTN, and 3. The inhibitory effect of apomorphine is observed following injection into several DA containing structures.
Keywords:GABA receptors  Dopamine receptors  Turning behavior  Substantia Nigra  Nigro-striatal system
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