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J Arnt

Publications and source records attributed to J Arnt.

89 records · Page 5Linked to original sources
PubMed1981

Differential reversal by scopolamine and THIP of the antistereotypic and cataleptic effects of neuroleptics.

Scopolamine reversed the neuroleptic-induced catalepsy and neuroleptic blockade of amphetamine-induced stereotypies in rats. The effect on catalepsy was the most pronounced. Butyrophenones were mainly sensitive to scopolamine reversal whereas the thioxanthenes cis-Z-flupentixol and piflutixol were not significantly influenced. THIP did not change the effects of cis-Z-flupentixol, fluphenazine and haloperidol. The relevance of these findings for the use of stereotypy and catalepsy tests as screening for antiscizophrenic and extrapyramidal side-effects, respectively, is discussed.

Amphetamine↗
PubMed1980

Intranigral GABA antagonists produce dopamine-independent biting in rats.

Behavioural effects following bilateral intranigral administration of GABA antagonists have been investigated. Bicuculline methiodide (BMI), picrotoxin and isopropylbicyclophosphate all induced biting behaviour, teeth-chattering and chewing. Sub-threshold doses for biting induced locomotor activity and sniffing. The strongest response was observed after injection into the caudal pars reticulata, whereas weaker effects were seen after injection into the rostral pars reticulata or the pars compacta. The biting induced by intranigral BMI was not antagonized by prior catecholamine depletion with reserpine plus alpha-methyl-p-tyrosine or by dopamine receptor blockade with haloperido. Concomitant intranigral injection of the GABA agonists muscimol and THIP, however, completely antagonized biting. Systemic GABAergic drugs also antagonized the BMI-induced biting: the benzodiazepine, diazepam and the GABA transaminase inhibitor, gamma-acetylenic GABE, were most effective, whereas muscimol was only partially effective and THIP was without effect. It is suggested that this animal model may be used for the evaluation of antidyskinetic drugs.

Aggression↗
PubMed1979

GABAergic and glycinergic mechanisms within the substantia nigra: pharmacological specificity of dopamine-independent contralateral turning behavior and interactions with other neurotransmitters.

The pharmacological specificity of the GABA agonist muscimol-induced contralateral turning behavior after unilateral injection into substantia nigra pars reticulata (SNR) has been studied. Muscimol-induced turning was antagonized by intranigral bicuculline methochloride (BMC) and picrotoxin, whereas antagonists of glycine, morphine, dopamine, noradrenaline, and serotonin were ineffective. Glycine induced a qualitatively similar turning behavior which was strychnine-sensitive but relatively BMC and picrotoxin-insensitive. Other drugs, including substance P, kainic acid, clonidine, oxymetazoline, serotonin, and carbachol, induced turning that could be dissociated from the effect of muscimol. Muscimol-induced turning was dopamine-independent, indicated by resistance to haloperidol (1 mg/kg), to pretreatment with reserpine (7.5 mg/kg) plus alpha-methyl-p-tyrosine (200 mg/kg), to haloperidol injections into the SNR, striatum and nucleus accumbens, and finally to kainic acid lesions of the striatum. 6-Hydroxydopamine lesions increased the efficacy of intranigral muscimol, while kainic acid lesions of the SNR antagonized muscimol. Muscimol-induced turning was inhibited by oxotremorine (0.25 mg/kg), by intranigral carbachol, and by apomorphine (0.1--0.5 mg/kg), but only moderately by intranigrally injected apomorphine. These data suggest specificity of GABA-agonist-induced contralateral turning and indicate an interaction between nigral GABA and other neurotransmitters, particularly dopamine and acetylcholine.

Animals↗
PubMed1979

Muscimol and related GABA receptor agonists: the potency of GABAergic drugs in vivo determined after intranigral injection.

Contralateral turning behaviour following unilateral intranigral injection of a large series of GABA analogues was investigated. The results indicated that the turning behaviour was induced stereospecifically and was selectively antagonized by the GABA antagonist bicuculline methochloride. The comparative potencies of a series of GABA agonists related to muscimol in general corresponded well to the affinity for 3H-GABA receptor sites and to the depressant action on single neurons using microelectrophoretic administration. However, the GABA agonists trans-aminocrotonic acid and 3-aminopropanesulphonic acid were much weaker than expected from in vitro studies. The GABA-uptake inhibitors nipecotic acid and guvacine showed only weak and short-lasting effects. The GABA-transaminase inhibitor gamma-acetylenic GABA showed delayed effects compared with the agonists which acted immediately. It is proposed that this behavioural effect may be a sensitive and quantitative method for evaluation of GABA agonists in vivo.

Animals↗
PubMed1978

Muscimol antagonizes morphine hypermotility without potentiation of analgesia.

Muscimol, a very potent and specific GABA agonist, strongly depressed characteristic morphine-induced locomotor activity. Muscimol induced only a very weak increase in the morphine analgesia measured in the hot plate test which perhaps could be a result of a freezing reaction. No effect on morphine analgesia was observed in the wire grid test. These results indicate that GABA differentially influences morphine stimulation and analgesia.

Analgesia↗
PubMedDate not supplied

Behavioural correlates to the dopamine D-1 and D-2 antagonists.

The acute dopamine (DA) receptor blockade of neuroleptics can be demonstrated in mice by antagonism of stereotypies induced by the DA-agonist methylphenidate and in rats by antagonism of stereotypies induced by the DA-agonists amphetamine or apomorphine. Neuroleptics such as the thioxanthene, cis(Z)-flupentixol, the phenothiazine, fluphenazine, the butyrophenone, haloperidol and the benzamide clebopride are equipotent behaviourally as well as clinically. Also the D-1 receptor-antagonist SCH 23390 has the same pharmacological effects. In a series of experiments where the methylphenidate-induced stereotyped gnawing in mice was inhibited by neuroleptics it was shown that the effect of butyrophenones was greatly attenuated by concomitant treatment with scopolamine and diazepam. Similar results were obtained in rats experiments. The effect of phenothiazines was less influenced and that of thioxanthenes and SCH 23390 remained nearly unchanged. Besides, a clear differentiation of these drugs was seen when they were tested in mice rendered supersensitive by 12 days treatment with different neuroleptics. In the withdrawal phase the decrease effects against methylphenidate were shown by increased ED50 values for methylphenidate antagonism and an increased response to methylphenidate. The thioxanthenes and SCH 23390 retained the ability to antagonize the stereotyped gnawing, the phenothiazines showed a reduced effect, whereas the butyrophenones showed both tolerance and cross tolerance to the stereotyped behaviour. This behavioural classification of neuroleptics into three different groups is comparable with the classification obtained by DA-receptor binding techniques in vitro.

Adenylyl Cyclases↗
PubMedDate not supplied

Prolonged treatment with the specific 5-HT-uptake inhibitor citalopram: effect on dopaminergic and serotonergic functions.

The effect of prolonged administration of the clinically effective and specific serotonin (5-HT)-uptake-inhibitor, citalopram, has been studied in rats on behavioural measures of dopaminergic (DA) and serotonergic activity and on DA D-2, 5-HT2, alpha 1- and beta-adrenergic receptor number and affinity in vitro. Thirteen days treatment with citalopram in the diet (40 mg/kg/day) did not change receptor binding for either of the ligands studied, although citalopram was detected in high concentrations in brain and plasma and induced a 75% depletion of 5-HT in whole blood. This citalopram dose-regimen was followed by a potentiated hypermotility response to d-amphetamine. Also DA-dependent hypermotility induced by methylphenidate and (+)-3-PPP was increased. In contrast, the 5-HT2-receptor mediated head shake syndrome induced by 1-5-HTP or quipazine was decreased after prolonged citalopram treatment. Two weeks oral bolus treatment (10 mg/kg once or twice daily) with the 5-HT-uptake-inhibitors citalopram, fluoxetine, zimelidine, cyanimipramine or paroxetine induced d-amphetamine potentiation, whereas amitriptyline, nortriptyline, imipramine, iprindole, and mianserin treatment showed no effect. It is suggested that d-amphetamine potentiation induced by citalopram is mainly dependent on DA mechanisms, and that this profile is characteristic for preferential 5-HT-uptake-inhibitors. The lack of correlation between behavioural effect and receptor changes was important. Since citalopram has been shown to have clinical antidepressant activity, it is concluded that down-regulation of beta-adrenoceptors is not a prerequisite for antidepressant action.

Animals↗