Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Climbing behaviour induced by apomorphine in mice: a potential model for the detection of neuroleptic activity. 2 33

Bilateral intra-accumbens 6-OHDA (2 micrograms in the presence of DMI and tranylcypromine, 14th postoperative day) enhanced the climbing responses of mice to apomorphine and 2-(N,N-dipropyl)amino-5,6-dihydroxytetralin causing parallel shifts of the normal log dose-response curves to the left. The enhancement of the apomorphine response was shown to be dependent on the dose of 6-OHDA, 0.5 micrograms being threshold and 2 micrograms maximum. Increased climbing was apparent by the 5th postoperative day, maximum by the 10th day, and was then maintained throughout the experimental period (6-8 weeks). 0.25-2 micrograms intra-accumbens 6-OHDA caused dose-related decreases in the dopamine content of mesolimbic areas (nucleus accumbens and tuberculum olfactorium) without causing significant changes in mesolimbic noradrenaline or striatal dopamine. In the absence of DMI/tranylcypromine, 2 and 4 micrograms 6-OHDA also decreased mesolimbic noradrenaline and striatal dopamine content. 16 micrograms 6-OHDA injected into the striatum (after DMI/tranylcypromine) decreased the striatal dopamine content by 85% (without altering mesolimbic dopamine or noradrenaline content) but this treatment failed to modify apomorphine climbing (2nd-12th postoperative days). Haloperiod, sulpiride, thioridazine, clozapine ad metoclopramide each caused a dose-dependent decrease in apomorphine climbing in both normal and 6-OHDA-treated mice. Haloperidol and metoclopramide were approximately equipotent in both groups of animals whilst sulpiride and thioridazine were approximately 4x more potent in the 6-OHDA-treated mice (the development of muscular hypotonia made an interpretation of clozapine effects difficult). The data indicate that an important role for the mesolimbic nucleus accumbens in the mediation of apomorphine climbing, and indicate that the antagonism by sulpiride and thioridazine may be specifically increased when mesolimbic mechanisms are rendered 'supersensitive'.
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PMID:The mesolimbic system, denervation and the climbing response in the mouse. 610 25