The bilateral intrastriatal administration of dopamine to guinea pigs pretreated with nialamide-induced dyskinesias characterized by gnawing, biting and licking reactions, acute twisting of the head and neck, whole body or head and neck rocking movements, and a hyperactive state. Hyperactivity was inhibited by the peripheral administration of large doses of many neuroleptic agents, e.g. haloperidol, fluphenazine, but only pimozide and oxiperomide inhibited the other forms of dyskinetic movements. This was not due to a peculiar depressant effect of these agents in the guinea pig since haloperidol was shown to be equipotent to oxiperomide and of greater potency than pimozide both in causing catalepsy and antagonising amphetamine sterotypy...

Adrenergic alpha-Antagonists↗

PubMedDate not supplied

Hyperactivity induced by injection of dopamine into the accumbens nucleus: actions and interactions of neuroleptic, cholinomimetic and cholinolytic agents.

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Animals↗

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Actions of sulpiride and tiapride in a simple model of anxiety in mice.

A two-compartment activity box is described in which the actions of anxiolytic compounds may be readily detected. The box is designed with a partition which divides a dimly-lit black area and a brightly-illuminated white area. Free access to each section is enabled by means of a small opening in the partition. Measures of locomotion and rearing are recorded as well as transitions from black to white and vice versa. Time spent in each section is also measured. In this situation mice demonstrated a clear preference for the dim black section, a finding not inconsistent with the nocturnal nature of this species. By contrast, treatment with diazepam (0.125-5 mg/kg) or triazolam (0.01-0.1 mg/kg) produced a significant increase in activity in the white section. Locomotion and rearing in the black section showed a corresponding decrease. Sulpiride (0.5-20 mg/kg) and tiapride (0.5-40 mg/kg) had similar effects. These actions would appear to be independent of their effects on general activity, as amphetamine (1.25-2.5 mg/kg) increased and haloperidol (0.05-0.2 mg/kg) decreased overall exploratory behaviour in a non-selective manner. These data suggest the "two-compartment activity box" to be a model sensitive to the actions of clinically-active anxiolytics.

Amphetamine↗

PubMedDate not supplied

1-methyl-4-phenylpyridine is neurotoxic to the nigrostriatal dopamine pathway.

Systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is neurotoxic to cerebral dopaminergic neurones in several animal species, and can cause parkinsonism in man. The mechanism of this action may be indirect. MPTP is oxidized in the brain to a pyridinium species, 1-methyl-4-phenylpyridine (MPP+)6. This oxidation is greatly decreased by inhibition of monoamine oxidase B6, as are the biochemical effects of MPTP in the mouse and its neurotoxicity in the monkey. We now show that MPP+ exerts a powerful neurotoxic action on the nigrostriatal dopamine system of the rodent.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMedDate not supplied

Cognitive enhancing actions of DuP 753 detected in a mouse habituation paradigm.

The potential of DuP 753, an angiotensin II receptor antagonist, to improve cognitive performance was assessed in a mouse habituation paradigm. On repeated daily testing DuP 753 (10.0 ng kg-1 p.o.) enhanced the basal cognitive performance of mice (decrease in latency to move from the light to the dark compartment and increases in the rears, line crossings and percentage of time spent in the dark compartment) and overcame the cognitive impairment induced by the administration of scopolamine (0.25 mg kg-1 i.p.). These findings further implicate the modulation of mental function by angiotensin II.

Angiotensin II↗

PubMedDate not supplied

Normal densities of 5-HT3 receptor recognition sites in Alzheimer's disease.

The present studies investigate the possible difference in 5-HT3 receptor recognition site density in amygdaloid and hippocampal homogenates from patients with Alzheimer's disease compared with age-matched controls. The 5-HT3 receptor recognition site radioligand [3H]-(S)-zacopride identified a comparable density of specific sites (defined by granisetron 10.0 microM) in tissues obtained from patients with Alzheimer's disease as compared to age-matched controls (amygdala, Bmax 41 +/- 4 and 43 +/- 9; hippocampus, Bmax 59 +/- 9 and 51 +/- 9 fmol mg-3 protein; tissue from Alzheimer's disease patients and age-matched controls, respectively, mean +/- s.e.m., n = 7-8). These results suggest that the density of 5-HT3 receptor recognition sites labelled by [3H]-(S)-zacopride are not altered in the amygdala and hippocampus of patients with Alzheimer's disease.

Aged↗

PubMedDate not supplied

Pharmacological properties and functions of central 5-HT3 receptors.

5-HT3 receptors or recognition sites have been located in the brain of many animal species and man, and are considered to mediate an increase in cation conductance. The functional relevance of the central 5-HT3 receptors is being established using selective 5-HT3 receptor antagonist ligands, which have been shown to modify behaviour in animal tests that is predictive of an action to reduce anxiety, schizophrenia and cognitive disorders. A remarkable feature of the effect of 5-HT3 receptor antagonists is their ability and potency to control a disturbed behaviour in the absence of effect on normal behaviour. This reveals an important role for 5-HT in different behaviours: indeed, the breadth of action of the 5-HT3 receptor antagonists may be indicative of the critical importance of 5-HT in the control of catecholaminergic, cholinergic and peptidergic systems throughout the forebrain. Precisely how such effects are achieved remains a significant investigative challenge, with the potential for novel therapeutic developments being a major goal.

Animals↗