Search Results - (Author, Cooperation:A. G. Hayes)

2011-03-19

American Association for the Advancement of Science (AAAS)

0036-8075

1095-9203

Biology

Chemistry and Pharmacology

Computer Science

Medicine

Natural Sciences in General

Physics

Atmosphere ; Extraterrestrial Environment ; *Methane ; *Saturn ; Spacecraft

2018-06-01

American Association for the Advancement of Science (AAAS)

0036-8075

1095-9203

Biology

Chemistry and Pharmacology

Geosciences

Computer Science

Medicine

Natural Sciences in General

Physics

Geochemistry, Geophysics, Planetary Science

1435-1463

Catalepsy ; fluphenazine ; sulpiride ; striatum ; phencyclidine ; Parkinson's disease ; MK801 ; CPP

Springer Online Journal Archives 1860-2000

Medicine

Summary Subcutaneous administration of fluphenazine elicits catelepsy that can be attenuated by the glutamate antagonists MK801 and phencyclidine (PCP). 3-[-(+)-2-carboxy piperazine-4-yl]-propyl-1-phosphanate (CPP) was found to be ineffective in this model. Intrastriatal injections of sulpiride or fluphenazine were also found to induce catalepsy which could be attenuated by MK801 and PCP. These results illustrate that nondopaminergic compounds might possibly be of value in the treatment of Parkinson's disease. Furthermore it was demonstrated that this paradigm can be utilized to investigate neurotransmitter interactions within the striatum. This was clearly emphasized by the observation that bilateral administration of MK801 into the striatum increased basal locomotor activity.

Electronic Resource

1435-1463

Catalepsy ; fluphenazine ; sulpiride ; striatum ; quinpirole ; Parkinson's disease ; L-DOPA ; amphetamine ; apomorphine ; SKF 38393

Springer Online Journal Archives 1860-2000

Medicine

Summary Catalepsy was observed in the rat following intrastriatal injections of the dopamine antagonists sulpiride or fluphenazine and after subcutaneous administration of fluphenazine. The neuroleptic-induced catalepsy was reversed by the classical anti-parkinsonian agent L-DOPA and by agents that function through dopamine systems such as d- and methamphetamine and the direct D2 receptor agonist quinpirole. The D1 agonist SKF 38393, and the D1/D2 agonist apomorphine, were ineffective in this model. These results support limited use of the rat catalepsy model for the screening of potential anti-parkinsonian compounds and indicate that this procedure can provide valuable information concerning striatal dopamine function.

Electronic Resource

1432-2072

Mesolimbic ; Nigro-striatal ; Atypical neuroleptics ; Typical neuroleptics ; Muscimol ; Behaviour

Springer Online Journal Archives 1860-2000

Medicine

Abstract Direct injections of muscimol into the ventral tegmental area (VTA) or substantia nigra zona reticulata (SNR) have been used to selectively stimulate the mesolimbic and nigro-striatal dopamine pathways respectively. Such injections induced locomotor activity, rearing, sniffing and in some animals an intermittent grooming response. These responses were rapid in onset, dose-related and relatively short lasting (〈40 min). Selective increases in dopamine turnover were seen in the nucleus accumbens and in the striatum following VTA and SNR injections of muscimol (100 ng) respectively. Haloperidol inhibited the behavioural consequences of VTA and SNR injections of muscimol with similar potency (ED50s 0.01–0.03 mg/kg IP), and fluphenazine did likewise (ED50s 0.05–0.16 mg/kg IP). However, thioridazine (ED50s VTA: 1.45–2.04 mg/kg IP, SNR 8.50–9.20 mg/kg IP) and in particular clozapine (ED50s VTA: 0.24–0.58 mg/kg IP, SNR: 6.10–9.70 mg/kg IP) were more potent at inhibiting the locomotor activity and sniffing responses due to VTA rather than SNR administered muscimol. Since dopamine D2 antagonists are believed to exert their anti-psychotic effects via an action on mesolimbic dopaminergic systems, and their ability to induce extrapyramidal side effects (EPS) is thought to be due to an action on nigro-striatal dopamine systems, these results suggest that the behavioural models described can be used to predict efficacy and side-effect liability of potential neuroleptic drugs.

Electronic Resource

1432-2072

Dopamine agonists ; 5HT antagonists ; Muscarinic antagonists ; Glutamate antagonists ; Marmoset

Springer Online Journal Archives 1860-2000

Medicine

Abstract A modified primate model of Parkinson's disease was developed to assess the effectiveness of various agents that act via dopamine, acetylcholine, serotonin or glutamate systems. Using a MPTP dosing regimen a reversible parkinsonian-like syndrome was produced in the marmoset. An obvious advantage of such a protocol is that it allows multiple drug studies to be undertaken in animals, without the need for prolonged anti-parkinsonian therapy to maintain their health. Results show that dopamine D2 agonists (bromocriptine, quinpirole, N,N-dipropyl,A,5,6-DTN, (+)3PPP and PHNO), anti-muscarinics (atropine, scopolamine and benztropine), in addition tol-DOPA and nomifensine, all reduced the bradykinesia induced by MPTP. The D1 agonist SKF-38393 and the partial dopamine agonist (−)3PPP were both ineffective. Finally, agents with potential therapeutic use in Parkinson's disease were also tested. However, a glutamate antagonist (MK801) and three serotonin antagonists (ritanserin, ketanserin and ICI 170,809) were all unable to alter the MPTP effects, at the doses used in our study.

Electronic Resource