Two experiments were performed to investigate the actions of the selective D1 blocker SCH 23390 and the selective D2 blocker sulpiride, on oral movements in rats; these were quantified by a human observer scoring vacuous chewing movements (VCMs), jaw tremor and head movements, as well as a computer analysis system which measured the amplitude and slope of each movement. In the first experiment it was found that both SCH 23390 and sulpiride decreased VCMs and head movements in a dose-dependent manner, with SCH 23390 more effectively decreasing head movements and sulpiride more effectively decreasing VCMs. In a second experiment, the effectiveness of these two drugs in blocking the actions of selective D1 (SKF 38393) and D2 (LY 171555) agonists was studied. The SKF 38393-induced increase in computer-scored movement was attenuated by both sulpiride and SCH 23390, whereas the LY 171555-induced decrease in VCMs was attenuated by sulpiride, while SCH 23390 exacerbated it. These findings, together with our earlier results, suggest a simple relationship of D1 receptors to oral movement, with increased activation resulting in increased oral movement and decreased activation resulting in decreased oral movement. The relationship of D2 receptors to oral movement shows a more complex pattern, with both stimulation and blockade decreasing oral movement. One possibility may be the existence of more than one subpopulation of D2 receptors mediating these effects.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1989

D1 and D2 dopamine receptor interactions with pilocarpine-induced oral activity in rats.

To investigate the relationship between dopamine (DA) and acetylcholine (ACh) systems in the control of oral movement, we studied the effects of specific D1 and D2 drugs on vacuous chewing movements induced by the muscarinic ACh agonist, pilocarpine. In previous experiments we found that when given alone, the D1 agonist SKF 38393 increased vacuous chewing and the D1 antagonist SCH 23390 decreased it, while both the D2 agonist LY 171555 (quinpirole) and the D2 antagonist sulpiride decreased vacuous chewing. In the present experiment, the effects of the D1 drugs had similar effects in rats concurrently given pilocarpine. In contrast, the effects of both of the D2 drugs were altered by pilocarpine. Surprisingly, the actions of D2 agonist and antagonist were affected in opposite ways. The effect of sulpiride in reducing oral movement activity was eliminated by pilocarpine, while the effect of LY 171555 in reducing oral movement was enhanced by pilocarpine.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1989

Effects of combined muscarinic and nicotinic blockade on choice accuracy in the radial-arm maze.

Acetylcholine (ACh) systems have been found to be crucial for the maintenance of accurate cognitive performance. A great variety of studies have shown that the muscarinic ACh receptor blocker scopolamine impairs choice accuracy in the radial-arm maze. Recently, it has been found that the nicotinic ACh receptor blocker mecamylamine also impairs radial-arm maze choice accuracy. In the present study, we investigated the effects of combined administration of these two ACh blockers. Scopolamine (0.15 mg/kg) and mecamylamine (10 mg/kg) each moderately impaired choice accuracy. Combined treatment with scopolamine and mecamylamine significantly decreased choice accuracy relative to either drug alone. This combination treatment lowered choice accuracy to chance levels. These data show that nicotinic and muscarinic blockade have at least additive effects in producing an anterograde memory deficit. Concurrent blockade of these two components of ACh systems may provide a better animal model of cognitive impairments due to the loss of cholinergic neurons, such as Alzheimer's disease.

Animals↗

PubMed1983

Phenytoin intoxication during treatment with parenteral miconazole.

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Aspergillosis↗