Behavioraleffects of intra-accumbens administration of the dopamine DA, receptor agonist (3,4-dihydroxyphenylimino)-2-imidazoline (DPI) were studied in freely moving rats. Three distinct areas were examined: core, shell and "shore," namely, the border region of the core and shell. DPI (5 pg) administered into the shell, but not areas ventral to the shell, increased chewing, tongue protrusion, sniffing, and grooming; it also induced abnormal oral behavior, namely, largeamplitude chewing.A similar dose of DPI administered into the core did not affect any (peri-)oral behavior, except sniffing. Because of methodological constraints the receptor specificity of the DPI effects was studied in rats with cannulas directed at the shore. DPI (5.0-l 0.0 pg) administered into the shore increased oral behavior dose dependently; however, the dose-effect curve varied per distinct type of oral behavior. The dopamine DA, receptor antagonist ergometrine attenuated the effect of DPI on tremor, chewing, and sniffing frequencies.Taken together, the data show that the effects of DPI were DA, receptor specific. The idea that the nucleus accumbens is a homogeneous structure is disappearing. During the last 10 years differences have been found between core and shell with respect to anatomy (Zaborsky et al., 1985; Voorn et al., 1989; Heimer et al., 1991;Berendse et al., 1992;Zahm and Brog, 1992; and others), receptor density (Bardo and Hammer, 199 l), pharmacology (Deutch and Cameron, 1992), and electrophysiology (Pennartz et al., 1992). Still, with respect to behavior of freely moving rats, no studies on differences between core and shell have been performed. Therefore, the aim of this study was to analyze the role of different parts of the nucleus accumbens in modulating behavior. The nucleus accumbens modulates oral behavior in rats (Bordi et al., 1989;Cools, 1990;Koshikawa et al., 1990 Koshikawa et al., , 1991Prinssen et al., 1992; Koene et al., 1993). It has been found that intra-accumbens administration of the dopamine DA, receptor Received Mar. 11, 1993; revised July 1, 1993; accepted Aug. 26, 1993. We express our gratitude to Dick Heeren for his valuable support with programming, and to Luuk Lubbers for the learning of operation techniques. agonist (3,4-dihydroxyphenylimino)-2-imidazoline (DPI) increases oral behavior in rats (Cools, 1990). In cats, the same drug (DPI) has been found to induce abnormal oral movements, namely, orofacial dyskinesias (OFD), when administered into a well-delineated striatal subarea (Cools et al., 1976; Spooren et al., 199 1). Accordingly, DPI was considered to be a valid tool to study the putative, differential involvement of the core and shell of the nucleus accumbens in oral behavior of freely moving rats. In the present investigation the behavioral effects of DPI injections into the core were compared with those elicited by DPI injections into the shell. The outcome of this study shows that administration of DPI (5 Kg) into the shell, but not the core, increased and induced oral behaviors. How...

Orofacial dyskinesia (OFD) is a disorder characterized by involuntary movements of the oral and facial muscles. OFD attacks can be elicited acutely in cats by local injections of dopaminergic agents into the anterodorsal part (r-CRM) of the caudate nucleus. Because the dopaminergic A8 cell group, being embedded in the retrorubral nucleus (RRN), gives rise to fibres which terminate in the r-CRM, two questions arose: (1) whether the A8 cell group forms part of the circuitry that directs and/or modulates OFD, and (2) whether GABA-ergic compounds in the RRN play a role in OFD, and if so, whether a pharmacological GABA-ergic intervention of the activity in the RRN modulates or mediates OFD. For this purpose, the activity of the RRN was manipulated with local injections of the GABA(A) agonist muscimol and antagonist bicuculline. These local injections into the RRN were subsequently combined with manipulations of dopamine transmission in the r-CRM with local injections of the selective DAi receptor agonist (3,4-dihydroxyphenylimino)-2-imidazoline. The present study shows that local injections of GABA-ergic compounds into the RRN do not elicit OFD attacks in cats, but can modulate oral behaviour elicited from the r-CRM. The latter effect is dose dependent and GABA-ergic specific.

The melanotrope cell of Xenopus laevis is innervated by nerve terminals that contain, among other transmitter substances, the neurotransmitter gamma-aminobutyric acid (GABA). Postsynaptically the melanotrope cell possess both GABAA and GABAB receptors. Activation of either receptor type leads to an inhibition of alpha MSH release from the cell. The present study concerns the functional significance of the existence of two types of GABA receptors on the melanotrope regarding two questions: 1) do the different receptor types have different effects on the melanotrope? and 2) can the endogenous ligand GABA differentially activate these receptors? Concerning the first question, we have tested the hypothesis that the GABAA receptor (a chloride ion channel) and the GABAB receptor (a G protein-coupled receptor negatively linked to adenylyl cyclase) may have differential effects on the sensitivity of the cell to stimulation by cAMP-dependent mechanisms. We show that treatments with either isoguvacine (GABAA agonist) or baclofen (GABAB agonist) inhibit intracellular Ca2+ oscillations and peptide secretion from melanotrope cells. Treatments known to increase intracellular cAMP in the melanotrope (e.g. use of the peptide sauvagine or the cAMP analog 8-bromo-cAMP) completely overcame the inhibition induced by baclofen, but not that caused by isoguvacine. We conclude that the GABAA and GABAB receptors have different effects on the Xenopus melanotrope cell by differentially affecting the sensitivity the cell shows to stimulation by cAMP-dependent mechanisms. Concerning possible differential activation of the receptor types, we found that we could use a membrane potential probe (from the bis-oxonol family) to differentiate between GABAA and GABAB receptor activation. Using this probe we showed that low GABA concentrations (< 10(-7) M) give a response indicative of the GABAB receptor, whereas at high GABA concentrations (> 10(-7) M), the GABAA receptor response predominates. We, therefore, conclude that GABA can differentially activate the two types of GABA receptors on the Xenopus melanotrope cell.

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