Search PubMed⌕ Search

Biomedical subjects

B Costall

Publications and source records attributed to B Costall.

292 records · Page 17Linked to original sources

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↗

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↗

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↗

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↗