Amphetamines administration

Amphetamine administration produces a marked increase in cortical dopamine, norepinephrine, and... 

The only evidence on chronic amphetamine administration and heightened aggressiveness derives from the studies, discussed earlier, on group-housed placid laboratory rats or mice. The behavioral validity of these phenomena under near-toxic dosage conditions, however, needs to be resolved. 

Eison, M.S. Wilson, WJ. and Ellison, G. A refillable system for continuous amphetamine administration Effects upon social behavior in rat colonies. Commun Psychopharmacol 2 151-157, 1978. 

Robinson, T.E., and Becker, J.B. Enduring changes in brain and behavior produced by chronic amphetamine administration A review and evaluation of animal models of amphetamine psychosis. Brain Res 11 157-198, 1986. 

Segal, D.S. Weinberger, S.B. Cahill, J. and McCunney, SJ. Multiple daily amphetamine administration Behavioral and neurochemical alterations. Science 207 904-906, 1980. 

The inhibition of firing of catecholamine neurons resulting from amphetamine administration is likely due to activation of somatodendritic autoreceptors. This causes a hyperpolarization of the somatodendritic membrane of both locus coeruleus noradrenergic and substantia nigra dopamine neurons, probably as a consequence of an increase in potassium conductance (Lacey et al. 1987 Williams et al. 1985). 

ANSWER We have looked at the globus pallidus in anesthetized animals, which appears to be uniformly increased by amphetamine administration. I might mention that Jean Walters has also looked at the globus pallidus in the behaving animals, and it is routinely increased by amphetamine administration. 

ANSWER I am not entirely sure, but people in my lab believe that the effects are related to two different populations of nerve cells, that those excited by amphetamine administration represent a different population, and... 

But there are those in my lab who believe that the excitation is being seen by a bias toward large cells and that they represent a large cell population in the neostriatum. I don t necessarily believe that. I don t know why, in the anesthetized animal, you can flip a nerve cell that is inhibited by amphetamine by increasing the dose. It has been postulated that the excitation is related to the occurrence of both the stereotyped behaviors, and that this may be provoked at doses that produce neurotoxicity. We have also done a number of studies looking at the neurotoxicity of amphetamine administration in animals, most of which replicate Lou Seiden s work. 

Gwen, F. Baker, H.F. Ridley, R.M. Cross, A.J. and Crow, T.J. Effect of chronic amphetamine administration on central dopaminergic mechanisms in the vervet. Psychopharmacology (Berlin) 74 213-216, 1981. 

Trulson, M.E., and Crisp, T. Behavioral effects of serotonergic and dopaminergic drugs in cats following chronic amphetamine administration. EurJPharmacol 99 3 3-324, 1984. 

Ellison, G. Eison, M.S. Huberman, H.S. and Daniel, F. Long-term changes in dopaminergic innervation of caudate nucleus after continuous amphetamine administration. Science 201 276-278, 1978. 

Other knockout models that could be used to validate candidate genes include mice that lack monoamine oxidase A (MAO-A), which have demonstrated altered behavior and alcohol tolerance [54]. Transgenic mice in which the dopamine transporter gene has been deleted show striking hyperactivity via enhanced persistence of dopamine which is not altered by cocaine or amphetamine administration [55]. Knockouts of the serotonin IB receptor are also available and are best used as models of vulnerability to drug abuse [56]. 

Liechti ME, Markou A (2007) Interactive effects of the mGlu5 receptor antagonist MPEP and the mGlu2/3 receptor antagonist LY341495 on nicotine self-administration and reward deficits associated with nicotine withdrawal in rats. Eur J Pharmacol 554 164-174 Lin D, Koob GP, Markou A (2000) Time-dependent alterations in ICSS thresholds associated with repeated amphetamine administrations. Pharmacol Biochem Behav 65 407-417... 

This disorder is characterised by inappropriate levels of activity, a high frequency of periods of frustration and distraction and hence inability to sustain attention and to concentrate on one activity for a prolonged period of time. A surprising finding is that amphetamine administration, which normally increases or facilitates activity, rapidly and markedly improves behaviour. Patients become calm and their alertness is enhanced. A drug that has been used is methylphenidate (Ritalin). One interesting and recent development is the improvement in the condition by supplementation of the diet with polyunsaturated fatty acids, particularly the omega-3 acids in fish oils (See Chapter 11). 

Some schizophrenic patients respond to amphetamine administration not with a deterioration but with an improvement in their state (Angrist et t//., 1982). 

In humans, both the d- and L-forms undergo hydroxylation and A-demethylation to their respective />hy dr ox y me thainphetamine and amphetamine metabolites. Amphetamine is the major active metabolite of methamphetamine. Under normal conditions, up to 43% of a D-methamphet-amine dose is excreted unchanged in the urine in the first 24 h and 4 to 7% will be present as amphetamine. In acidic urine, up to 76% is present as parent drug10 compared with 2% under alkaline conditions. Approximately 15% of the dose was present as /7-hydroxymethamphetamine and the remaining minor metabolites were similar to those found after amphetamine administration. Urine concentrations of methamphetamine are typically 0.5 to 4 mg/L after an oral dose of 10 mg. However, methamphetamine and amphetamine urine concentrations vary widely among abusers. Lebish et al.11 reported urine methamphetamine concentrations of 24 to 333 mg/L and amphetamine concentrations of 1 to 90 mg/L in the urine of methamphetamine abusers. 

Barnett, J., Kuczenski, R. (1986). Desensitization of rat striatal dopamine-stimulated adenylate cyclase after acute amphetamine administration. Journal of Pharmacology and Experimental Therapeutics, 237, 820—825. 

Roseboom PH, Hewlett GHK, Gnegy ME (1990) Repeated amphetamine administration alters the interaction between Dl-stimulated adenylyl cyclase activity and calmodulin in rat striatum. J Pharmacol Exp Ther 255 197-203. 

Rrivanek JA, McGaugh JL (1969) Facilitating effects of pre- and post-trial amphetamine administration on discrimination learning in mice. Agents Actions 1 36-42. 

Kendrick WC, Huii AR, Knochei JP. Rhabdomyoiysis and shock after intravenous amphetamine administration. Ann intern Med 1977 86 381-387. 

In addition to acute effects, however, prolonged usage of amphetamines (and other psychostimulants) can produce an "amphetamine psychosis." This syndrome was first clearly documented by Connell (25) and is regarded as very similar to paranoid schizophrenia, characterized by "paranoid psychosis with ideas of reference, delusions of persecution, auditory and visual hallucinations in a setting of clear consciousness" (25). The psychosis clears quickly after the drug is withdrawn. Psychosis has been induced experimentally in normal subjects by continuous amphetamine administration (26). Amphetamine psychosis has... 

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