Topographical resolution of jaw movements mediated by cyclase- vs. non-cyclase-coupled dopamine D(1)-like receptors: studies with SK&F 83822.

This study examined the effects on orofacial movement topography of SK&F 83822 ([R/S]-6-chloro-7,8-dihydroxy-3-allyl-1-[3-methylphenyl]-2,3,4,5-tetrahydro-1H-3-benzazepine), which stimulates dopamine D(1)-like receptors coupled to stimulation of adenylyl cyclase (AC) but not phosphoinositide (PI) hydrolysis, in comparison with SK&F 83959 ([R/S]-3-methyl-6-chloro-7,8-dihydroxy-1-[3-methyl-phenyl]-2,3,4,5-tetrahydro-1H-3-benzazepine), which stimulates PI hydrolysis but not AC. SK&F 83822 alone induced chattering, while SK&F 83959 alone exerted little effect. SK&F 83822 and SK&F 83959 each in combination with the dopamine D(2)-like agonist quinpirole resulted in synergistic induction of non-chattering movements with tongue protrusions. These effects were blocked by the dopamine D(1)-like receptor antagonist SCH 23390 ([R]-3-methyl-7-chloro-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine). However, the dopamine D(2)-like receptor antagonist YM 09151-2 (cis-N-[1-benzyl-2-methyl-pyrrolidin-3-yl]-5-chloro-2-methoxy-4-methylaminobenzamide) exerted a biphasic effect on synergism with SK&F 83822: chattering was initially released but antagonised thereafter. Only antagonism was seen for synergism with SK&F 83959. While both AC- and PI-coupled dopamine D(1)-like receptors participate in synergistic dopamine D(1)-like:D(2)-like receptor interactions, topographically specific synergistic and oppositional dopamine D(1)-like:D(2)-like interactions evident with SK&F 83822 reflect the involvement primarily of D(1)-like receptors coupled to AC rather than PI.

Role of GABA(A) receptors in the retrorubral field and ventral pallidum in rat jaw movements elicited by dopaminergic stimulation of the nucleus accumbens shell.

The role of gamma-aminobutyric acid (GABA)(A) receptors in the retrorubral field in the production of rat repetitive jaw movements was examined, as this nucleus receives a GABAergic, inhibitory input from the nucleus accumbens and is connected with the parvicellular reticular formation, a region that is directly connected with the orofacial motor nuclei. The GABA(A) receptor antagonist bicuculline (150 ng/0.2 microl per side) significantly produced repetitive jaw movements when injected bilaterally into the retrorubral field, but not the ventral pallidum. The effects of bicuculline were GABA(A) receptor specific, because the effects were abolished by muscimol, a GABA(A) receptor agonist, given into the same site. The bicuculline-induced jaw movements differed qualitatively from those elicited by injection of a mixture of (+/-)-6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol (SKF 82958; 5 microg) and quinpirole (10 microg), agonist at dopamine D1 and D2 receptors respectively, into the nucleus accumbens shell. Nevertheless, bilateral injections of muscimol (10 ng, 25 ng and 50 ng/0.2 microl per side) into the retrorubral field significantly inhibited jaw movements evoked by the dopamine D1/D2 receptor stimulation in the nucleus accumbens shell. Bilateral injections of bicuculline (50 ng and 150 ng/0.2 microl per side) also reduced the dopamine D1/D2 receptor-mediated jaw movements. Essentially similar effects were obtained when muscimol and bicuculline were given into the ventral pallidum, a region that is also known to receive GABAergic inhibitory inputs from the nucleus accumbens. In conclusion, GABA(A) receptor blockade in the retrorubral field elicits characteristic repetitive jaw movements, and the GABA(A) receptors in that region as well as in the ventral pallidum modulate the accumbens-specific, dopamine D1/D2 receptor-mediated jaw movements.

Decreased postsynaptic dopaminergic and cholinergic functions in the ventrolateral striatum of spontaneously hypertensive rat.

Dopamine and acetylcholine receptor functions in spontaneously hypertensive rats (SHR) and in control progenitor Wistar-Kyoto (WKY) rats were assessed, using dopamine D1-like/D2-like receptor-mediated and acetylcholine receptor-mediated jaw movements as readout parameters. Spontaneous behaviours such as locomotor activity, vacuous chewing, grooming, sniffing and rearing occurred significantly more in SHR than in WKY rats. In the anaesthetised rats, a mixture of SKF 38393 (5 micrograms), a dopamine D1-like receptor agonist, and quinpirole (10 micrograms), a dopamine D2-like receptor agonist, readily produced repetitive jaw movements in WKY rats, but not SHR, when bilaterally injected into the ventrolateral striatum; such injections into the nucleus accumbens shell were ineffective in each strain. Bilateral injections of carbachol (2.5 micrograms each side), an acetylcholine receptor agonist, into the ventrolateral striatum elicited repetitive jaw movements in both SHR and WKY rats, but to a far less degree in SHR. The present study demonstrates that spontaneous behaviours are enhanced in SHR, and that postsynaptic dopamine D1-like/D2-like receptors and acetylcholine receptors in the ventrolateral striatum of SHR are hyposensitive when compared to those of WKY rats.