Methamphetamine effects

ANSWER Yes, 6-hydroxydopamine by itself elevates neurotensin levels. When you combine it with methamphetamine, you do not get any additivity. It is just a 6-hydroxydopamine action. It is a bit complicated to interpret, but it appears that it is still the nigral striatal dopamine pathway that is mediating the methamphetamine effect. 

Schmidt, C.J. and Gibb, J.W., Role of the dopamine uptake carrier in the neurochemical response to methamphetamine effects of amfonelic acid, Eur. J. Pharmacol., 109, 73, 1985. 

Logan BK (2002) Methamphetamine-effects on human performance and behavior. Forensic Sd Rev 14 133-151... 

Sonsalla, P.K. Gibb, J.W. and Hanson, G.R. Nigrostriatal dopamine actions on the D2 receptors mediate methamphetamine effects on the striatonigral Substance P system. Neuropharmacology 25 1221-1230, 1986. 

Martin WR, Sloan JW, Sapira JD, et al Physiologic, subjective, and behavioral effects of amphetamine, methamphetamine, ephedrine, phenmetrazine, and methylphenidate in man. Clin Pharmacol Ther 12 245-258, 1971 McCormick TC Jr, McNeil TW Acute psychosis and Ritalin abuse. Tex State J Med... 

In humans, a comparative examination of the positive reinforcing effects of solvents showed that among inhalant-dependent subjects, solvents induced a more intense sensation of pleasant feelings than that induced by alcohol and nicotine in subjects addicted to these substances (Kono et al. 2001). Solvent-dependent subjects reported pleasant feelings comparable to those reported by stimulant-dependent subjects after use of methamphetamine. However,... 

Tolerance is characterized by reduced responsiveness to the initial effects of a drug after repeated exposure or reduced responsiveness to a related compound (i.e., cross-tolerance). Animal studies have not provided conclusive evidence of tolerance to the effects of the centrally active compounds in toluene or trichloroethane (Moser and Balster 1981 Moser et al. 1985). Observations in humans, on the other hand, have documented pronounced tolerance among subjects who chronically inhale substances with high concentrations of toluene (Glaser and Massengale 1962 Press and Done 1967) and butane (Evans and Raistrick 1987). Kono et al. (2001) showed that tolerance to the reinforcing effects of solvents is comparable to that conditioned by nicotine but less intense than that reported with alcohol or methamphetamine use. 

The reinforeing properties of psychomotor stimulants have also been linked to the aetivation of eentral dopamine neurons and their postsynaptie reeep-tors. When the synthesis of eatecholamines is inhibited by administering alpha-methyl-para-tyrosine, an attenuation of the subjective effeets of euphoria assoeiated with psyehomotor stimulants oeeurs in man (Jonsson et al. 1971), and a bloekade of the reinforeing effects of methamphetamine occurs in animals (Pickens et al. 1968). Furthermore, low doses of dopamine antagonists will increase response rates for intravenous injections of h-amphetamine (Risner and Jones 1976 Yokel and Wise 1975 Yokel and Wise 1976). 

Hotchkiss, A.J. Morgan, M.E. and Gibb, J.W. The long-term effects of multiple doses of methamphetamine on neostriatal tryptophan hydroxylase, tyrosine hydroxylase, choline acetyltransferase and glutamate decarboxylase activities. Life Sci 25 1373-1378. 1979. 

METHAMPHETAMINE STUDIES METH Effects on the Dopaminergic System... 

The main reason for my suspicion is that in the experiment with AMT where the effeet of methamphetamine on tyrosine hydroxylase activity can be bloeked and then reinstituted by eoadministering /-dopa, one would prediet that if one is really talking about neurotoxie effects, then one ought to be able to observe the same ehanges 2 weeks later. 

Bakhit, C. Morgan, M.E. Peat, M.A. and Gibb. J.W. Long-term effects of methamphetamine on the synthesis and metabolism of 5-hydroxytryptamine in various regions of the rat brain. Neuropharmacology 20 1135-1140, 1981. 

Fibiger, H.C., and McGeer, E.G. Effect of acute and chronic methamphetamine treatment on tyrosine hydroxylase activity in brain and adrenal medulla. Eur J Pharmacol 16 176-180, 1971. 

Peat, M.A. Warren, P.F. Bakhit, C. and Gibb, J.W. The acute effects of methamphetamine, amphetamine and p-chloroamphetamine on the cortical serotonergic system of the rat brain Evidence for differences in the effects of methamphetamine and amphetamine. Eur J Pharmacol 116 11-16, 1985. 

This chapter discusses the responses of these extrapyramidal neuropeptide systems to the amphetamine analogs methamphetamine (METH), methylene dioxyamphetamine (MDA), and methylenedioxymethamphetamine (MDMA). These dmgs were selected for this study because they represent somewhat diverse mechanisms of action. While all three agents are able to enhance extrapyramidal serotonergic activity (Schmidt et al. 1987). only METH has been characterized as a substantial stimulant of the DA system. The effects of MDA and MDMA on extrapyramidal DA systems have not been well elucidated. Thus, evaluating and comparing the responses of the SP, NT, and Dyn extrapyramidal systems to these dmgs will help to determine the nature of the DA responses to METH, MDA, and MDMA administrations. 

The behavioral effects of amphetamine, methamphetamine, MDMA, MDA, p-chloroamphetamine, and fenfluramine are not identical. Except for the last drug, all can cause some degree of behavioral stimulation, but exact behavioral effects differ markedly. More complete definition of their behavioral differences is a prerequisite to a better understanding of the mechanism(s) of these drugs. 

During the 1970s, evidence accumulated that amphetamine and methamphet-amine could also be neurotoxic (Ellison et al. 1978 Hotchkiss and Gibb 1980 Wagner et al. 1980). The effects of amphetamine seem mostly limited to dopamine neurons, whereas methamphetamine affects dopamine and serotonin neurons (Warren et al. 1984). Most recently, MDMA and MDA have been shown to produce neurotoxicity toward brain serotonin neurons much like that of the halogenated amphetamines (Ricaurte et al. 1985 Stone et al. 1986). 

Commins et al. (1987) have also reported the formation of 5,6-dihydroxy-tryptamine in rat hippocampus after a single, high doses of methamphetamine. They suggested that the formahon of 5,6-dihydroxytryptamine, a known neurotoxie substance, may mediate the neurotoxie effects of methamphetamine toward serotonergic nerve terminals. 

Role of dopamine in the neurotoxic effects of methamphetamine. J Pharmacol Exp Ther 233 539-544, 1985. 

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