Differential effects of (3,4-dihydroxyphenylamino)-2-imidazoline (DPI) on hyperactivity responses to dopamine agonists injected in the nucleus accumbens.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to B Costall.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Apomorphine and the putative dopamine agonist, 2-(N, N-dipropyl)-amino-5, 6-dihydroxytetralin induced dose-dependent climbing behaviour in the mouse which was measured in wire mesh lined cages as the percentage of time spent climbing in the 30 min period following the first climb and as the maximum time spent in a single climb throughout the drug effect. These These two measures were generally found to parallel excepting when the interacting agent caused muscular hypotonia. All potential interacting agents were given as pretreatments to determine changes in motor function which may interfere with the climbing induced by 1.0 mg/kg s.c. apomorphine. The possibility of a change in the apomorphine response to a sterotyped biting, which would also interfere with climbing, was also considered. Excluding these non-specific changes, climbing behaviour was shown to be antagonised, dose-dependently, by low doses of typical and atypical neuroleptic agents (haloperidol, fluphenazine, loxapine, pimozide, oxiperomide, clozapin, thioridazine, sulpiride, tiapride and metoclopramide) but not specifically by other psychoactive agents. Climbing behaviour was modified by serotonergic agents; the agonist quipazine reduced or abolished, whilst the antagonists, methysergide and cyproheptadine, enhanced the response. Picrotoxin specifically reduced climbing behaviour but sodium valproate exerted non-specific effects, precluding conclusions as to a GABA involvement. Cholinergic and noradrenergic involvements with climbing were also apparently eliminated by the ineffectiveness of atropine, aceperone, piperoxan and propranolol. The involvement of serotonin with climbing was extended to the actions of the neuroleptics: the antagonistic effects of typical neuroleptics (haloperidol, fluphenazine, loxapine) were markedly enhanced by combination with methysergide or cyproheptadine whilst the effects of clozapine, sulpiride and thioridazine were significantly reduced. The actions of metoclopramide, oxiperomide, pimozide and tiapride were not generally modified by such combinations. These differences are discussed in terms of differential abilities to induce extrapyramidal disturbances and the mouse climbing model is forwarded as a test with potential to detect antipsychotic agents of different activity spectra.
The activities of oxiperomide and tiapride were compared with those of control "neuroleptic" agents in the dyskinesia model using 2-(N,N-dipropyl)amino-5,6-dihydroxytetralin to induce peri-oral movements, in order to determine whether the differential activities (oxiperomide and tiapride being comparatively more effective as antagonists) may involve striatal gabaminergic and serotonergic mechanisms. The peri-oral movements induced by the 2-aminotetralin compound (0.05 mg/kg s.c.) were antagonised by intrastriatal GABA (2.5--10 microgram bilateral) and serotonin (25--100 microgram bilateral). Sodium valproate (i.p.) had little effect but 1.25 mg/kg s.c. quipazine abolished the peri-oral dyskinesia. Subthreshold doses (i.p.) of oxiperomide and tiapride synergised with subthreshold intrastriatal doses of both GABA and serotonin, and with s.c. quipazine, to antagonise the peri-oral movements induced by the 2-aminotetralin compound. Subthreshold doses of haloperidol, sultopride, metoclopramide and pimozide failed to consistently antagonise peri-oral movements when similarly combined with GABA, serotonin or quipazine. It is suggested that, in addition to their known action on cerebral dopamine mechanisms, oxiperomide and tiapride may modify abnormal peri-oral movements by modulation of striatal gabaminergic and serotonergic mechanisms.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The title compounds have been synthesized and evaluated for emetic effects in the dog, actions on the cardioaccelerator nerve in the cat, pecking in pigeons, and for behavioral effects following both peripheral and direct intracerebral injection into the nucleus accumbens and caudate-putamen of the rat. Generally, in the series studied, the N,N-diethyl and N,N-di-n-propyl congeners of dopamine displayed notably high degrees of activity. However, the test compounds exerted differing effects on peripheral and central dopamine receptors and in the area postrema. Differentiations of the activities of the different homologues within the brain were also shown.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.