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A Hashim

Publications and source records attributed to A Hashim.

47 records · Page 3Linked to original sources
PubMed1989

Chronic L-deprenyl does not alter the restoration of striatal dopamine in MPTP-lesioned mice.

The present study examined the effect of chronic L-deprenyl on dopaminergic terminal function after mouse striatal terminals were lesioned with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 2 x 30 mg/kg s.c.). In the MPTP-lesioned mice, the level of dopamine was decreased by 59% 1 week after MPTP administration and by 22% at 16 weeks. Chronic administration of L-deprenyl (0.1 mg/kg, once weekly for up to 16 weeks) did not alter striatal dopamine metabolism, although monoamine oxidase B activity was reduced by 50% during this 16-week period, and did not alter the rate of restoration of the level of striatal dopamine.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1988

Effect of chronic oral nicotine on dopaminergic function in the MPTP-treated mouse.

Although epidemiological studies have suggested a lower incidence of Parkinson's disease in cigarette smokers, repeated exposure to cigarette smoke or nicotine does not protect against neurotoxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Since there is some evidence that nicotinic antagonists, nicotine, and neurotransmitters may have tropic effects on neurite outgrowth, the present study examined the effects of chronic nicotine administration for 16 weeks (in drinking water; 5 mg/kg consumed per day) on the rate of terminal recovery after striatal lesioning with MPTP (2 x 30 mg/kg, s.c.). Terminal recovery, as measured by the rate of recovery in the level of striatal dopamine, was not affected by nicotine. Monoamine oxidase-B activity was not reduced by MPTP, nor did nicotine affect its activity in striatal homogenates.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1988

Ascorbic acid and striatal transport of [3H] 1-methyl-4-phenylpyridine (MPP+) and [3H] dopamine.

The inhibition of uptake of [3H] dopamine and [3H] 1-methyl-4-phenylpyridine (MPP+) was examined in mouse striatal synaptosomal preparations. Kinetic analysis indicated that ascorbic acid is a noncompetitive inhibitor of [3H] MPP+ uptake. No inhibition of [3H] dopamine uptake is observed. The dopamine uptake blockers, GBR-12909, cocaine, and mazindol strongly inhibit (IC50 less than 1 uM) both [3H] dopamine and [3H] MPP+ transport. Nicotine, its metabolites, and other tobacco alkaloids are weak inhibitors (IC50 greater than 1 mM) except 4-phenylpyridine and lobeline, which are moderate inhibitors (IC50 = 3 to 40 uM) of both [3H] dopamine and [3H] MPP+ uptake. These similarities in potencies are in agreement with the suggestion that [3H] MPP+ and [3H] dopamine are transported by the same carrier. The differences observed in the alteration of dopaminergic transport and mazindol binding by ascorbic acid suggest that ascorbic acid's effects on [3H] MPP+ transport are related to translocation and/or dissociation processes occurring subsequent to the initial binding event.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1987

Behavioral and biochemical effects of nicotine in an MPTP-induced mouse model of Parkinson's disease.

This study examined the effects of nicotine on locomotor activity and on the level of dopamine (DA) and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum and olfactory tubercle of mice that had been treated with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP significantly lowered the spontaneous locomotor activity 1-2 weeks and 2 months after 2 injections of MPTP (30 mg/kg SC, 24 hr apart) in young adult (3 months) and old mice (22-24 months old). The effect of nicotine on locomotion was biphasic; an initial stimulation of locomotor (0-5 min after nicotine) followed by a depressant period lasting from 5 to 20 min after injection. Tolerance to the depressant effect of nicotine developed after the 5th day of daily injections of nicotine (0.4 mg/kg SC, twice daily). Tolerance did not occur by day 8 to the initial stimulatory effect of nicotine. A similar effect of nicotine on locomotor activity was seen in mice treated with MPTP. The levels of DOPAC and HVA in the striatum were reduced by about 20% in the chronic nicotine-treated animals. The levels of DOPAC, DA, and HVA were reduced in the MPTP-treated mice; however, acute and chronic nicotine did not cause an additional change in the amine levels. The results suggest that nicotine has an influence on locomotor activity in MPTP-treated mice and that this effect is not due to changes in DA receptor activity in the striatum caused by chronic nicotine.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

Effect of amphetamine on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity in mice.

Amphetamine has been shown to either potentiate or protect against MPTP neurotoxicity. The time course of changes in dopamine and its metabolites was examined after MPTP, amphetamine, or MPTP plus amphetamine administration. Results suggest that under conditions of granular depletion and release of dopamine by 10 mg/kg amphetamine, increased MPTP neurotoxicity occurs. Amphetamine injections at 2-5 mg/kg prevents the decline in dopamine possibly by blockade of the uptake of MPP+, rather than by an inhibition of monoamine oxidase.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

Effect of nicotine and amphetamine on the neurotoxicity of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice.

The present results show the potentiating effect of amphetamine on the ability of MPTP to destroy dopaminergic neurons in striatum of the mouse. A single injection of MPTP (8 mg/kg, retro-orbital) reduced the binding of [3H]mazindol, a marker for dopamine terminals, by 24%. When D-amphetamine (10 mg/kg, s.c.) was given 20 min prior to MPTP, the binding of [3H]mazindol, measured 3-5 days later, was reduced by 58%. It is proposed that the mechanism of this potentiation primarily involves an increased release of dopamine by D-amphetamine, and free radical-mediated processes. Although nicotine also releases dopamine from the striatum, no effect was observed when it was administered prior to MPTP. The lack of effect is probably related to short duration of action of nicotine and the modest effect on release of dopamine as compared to that of amphetamine.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1985

Protection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity by the antioxidant ascorbic acid.

Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 2 X 8 mg/kg retro-orbital) to BALB/cBy mice reduced [3H]mazindol binding to striatal membranes by 50%. Reactive oxygen derivatives have been suggested to be involved in MPTP neurotoxicity; therefore we examined the effects of ascorbic acid (an antioxidant). Ascorbic acid (100 mg/kg) given 20 min prior to MPTP administration appreciably prevented the reduction of [3H]mazindol binding. The involvement of oxidative processes in the mechanism of MPTP neurotoxicity may suggest a relationship to the etiology of Parkinson's disease, and the possible benefit of treatment with ascorbic acid.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1985

Comparison of [3H]nicotine and [3H]acetylcholine binding in mouse brain: regional distribution.

In a continuing study of nicotine binding sites, we determined the relative amount of nicotine binding and acetylcholine binding in various brain regions of C57/BL and of DBA mice. Although midbrain showed the highest and cerebellum the lowest binding for both [3H]nicotine and [3H]acetylcholine, the ratio of nicotine to acetylcholine binding showed a three-fold regional variation. Acetylcholine inhibition of [3H]nicotine binding indicated that a portion of nicotine binding was not inhibited by acetylcholine. These results indicate important differences between the binding of (+/-)-[3H]nicotine and that of [3H]acetylcholine.

Acetylcholine↗
PubMed1984

Reduction of dopamine uptake and cocaine binding in mouse striatum by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

Administration of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (NMPTP) (daily injections of 8 mg/kg for 5 days via tail vein) reduced [3H]dopamine uptake in striatal synaptosomes by 63% and reduced [3H]cocaine binding to striatal membranes by 61%. [3H]Cocaine binding was not affected in olfactory tubercle, suggesting a selective effect of NMPTP on the nigro-striatal but not on the mesolimbic dopaminergic system. The destruction of dopamine terminals in the striatum did not alter (up-regulate) [3H]spiroperidol binding. The results suggest that NMPTP causes a degenerative destruction of the striatal dopamine pathway and that NMPTP may be useful in developing a rodent model of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1984

Endogenous material in brain inhibiting [3H]nicotine and [3H]acetylcholine binding.

The supernatant obtained from mouse brain homogenates contains material that inhibits the saturable binding of [3H]nicotine in mouse cerebral cortex. This inhibitory material was further purified by heat denaturation, ultrafiltration through an Amicon PM-10 membrane filter, and gel chromatography on Sephadex G-10. The material inhibited the binding of [3H]acetylcholine with the same potency as it did that of [3H]nicotine. It also had some affinity for the sites that specifically bind [3H]D-Ala, D-Leu enkephalin, but had much lower affinity for the binding sites for [3H]quinuclidinyl benzilate (QNB), [3H]spiroperidol, [3H]naloxone, or [3H]imipramine. Acid hydrolysis destroyed the activity. These preliminary results suggest the presence in brain of "nicotinelike" substances, one of which may be the endogenous ligand for the sites that specifically bind [3H]nicotine.

Acetylcholine↗