Amphetamines behavioral effects

The various stimulants have no obvious chemical relationships and do not share primary neurochemical effects, despite their similar behavioral effects. Cocaines chemical strucmre does not resemble that of caffeine, nicotine, or amphetamine. Cocaine binds to the dopamine reuptake transporter in the central nervous system, effectively inhibiting dopamine reuptake. It has similar effects on the transporters that mediate norepinephrine and serotonin reuptake. As discussed later in this chapter in the section on neurochemical actions mediating stimulant reward, dopamine is very important in the reward system of the brain the increase of dopamine associated with use of cocaine probably accounts for the high dependence potential of the drug. 

Stimulants induce both tolerance and sensitization to their behavioral effects. Tolerance develops to the anorectic and euphoric effects of stimulants (Schuster 1981) however, chronic intermittent use of low doses of stimulants delays the development of tolerance. With the doses commonly used in clinical practice, patients treated for narcolepsy or for depressive or apathetic states find that the stimulant properties usually persist without development of tolerance however, the persistence of antidepressant effects remains a matter of controversy. Sensitization has been linked to the development of amphetamine-induced psychosis (Yui et al. 1999). Sensitization to the induction of psychosis is suggested because psychosis is induced by progressively lower doses and shorter periods of consumption of amphetamine following repeated use over time (Sato 1986). Sensitization for amphetamine-induced psychosis may persist despite long periods of abstinence. 

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... 

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. 

Holtzman, S.G. Behavioral effects of separate and combined administration of naloxone and J-amphetamine. J Pharmacol Exp Ther 189 51-60. 1974. 

Ridley, R.M. Baker, H.F. and Scraggs, P.R. The time course of the behavioral effects of amphetamine and their reversal by haloperidol in a primate species. Biol Psychiatry 14 753-765, 1979. 

Schirring, E., and Hecht, A. Behavioral effects of low, acute doses of (/-amphetamine on the dyadic interaction between mother and infant vervet monkeys (Cercopithecus aethiops) during the first six postnatal months. Psychopharmacology 64 219-224. 1979. 

Neurochemical Mechanisms Involved in Behavioral Effects of Amphetamines and Reiated Designer Drugs... 

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. 

Behavioral Effects of Amphetamines How Useful, What Mechanisms ... 

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. 

Metaphit administered ICV prior to PCP administered ICV antagonized PCP induction of stereotyped behavior and ataxia up to 5 days after metaphit pretreatment. The antagonism of the behavioral effects of PCP by metaphit was dose dependent as is shown in figure 4. Furthermore, this antagonism by metaphit is specific as metaphit pretreatment ICV did not antagonize amphetamine-induced stereotyped behavior and could be prevented by pretreating rats with PCP just prior to metaphit administration. These results indicate that acylation of PCP receptors results in decreased ability of PCP to induce stereotyped behavior. 

The administration of low doses of PCP to rodents induces hyperactivity and stereotypy (Chen et al. 1959 ). The observation that neuroleptics such as chlorpromazine, haloperidol, and pimozide, and adrenolytics such as alpha-methyl paratyrosine antagonize these behavioral effects of PCP suggests that they are mediated by facilitation of central dopaminergic neurotransmission (Murray and Horita 1979). The actions of PCP on central dopaminergic neurotransmission may be similar to amphetamine. A dose of PCP (2.5 mg/kg) in rats, which has no effects when given alone, enhances the behavioral effects of 1 and 3 mg/kg of d-amphetamine (Balster and Chait 1978). PCP, like dopamine, has also been shown to suppress plasma prolactin (Bayorh et al. 1983). However, the firm establishment of an excl usive relationship between dopamine neuro-transmission and PCP effects is difficult because of the prominent interactions of this drug with other neurotransmitter systems. 

Commissaris, R. L., Lyness, W. H., Moore, M. E., and Rech, R. H. (1980) Enhancement of the behavioral effects of 2,5-dimethoxy-4-methyl-amphetamine (DOM) by pretreatment with p-chlorophenylalanine. Pharmacol. Biochem. Behav., 13 605-608. 

Sloviter, R. S., Drust, E. G., and Connor, J. D. (1978) Evidence that serotonin mediates some behavioral effects of amphetamine. J. Pharmacol. Exp. Ther., 206 348-352. 

A second, more extensive experiment involved oral administration of three daily doses (100 mg/kg) of parachlorophenylalanine (PCPA). This tryptophan hydroxylase inhibitor (47), like reserpine, enhanced the behavioral effects of LSD (13) moreover, hypersensitivity occurred when 5-HT, but not other monoamine, concentrations were below normal in both forebrain and hindbrain (13). That is, effects were observed at 5 and 12 days (when 5-HT was depleted to 10-20% and 60-70% of normal) but not at 21 days (when 5-HT had returned to normal). Control experiments (13) indicated that (a) the interaction of PCPA, 5-HT, and LSD was probably not caused by generalized hyperactivity or hyperirritability sometimes seen after PCPA (73) (b) PCPA does not affect threshold doses of other psychoactive but nonserotonergic compounds, such as d-amphetamine (0.3 mg/kg) and (c) pretreatment with a-methylparatyrosine, a tyrosine hydroxylase inhibitor which depletes catecholamines rather than indoleamines, does not alter sensitivity to LSD. 

Rothman RB Baumarm MH (2006). Balance between dopamine and serotonin release modulates behavioral effects of amphetamine-type drugs. Annals of the New York Academy of Sciences, 1074, 245-60... 

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