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At least 37 records · Page 2Linked to original sources
PubMed2001

The purinergic P2 receptor antagonist pyridoxalphosphate-6-azophenyl-2'4'-disulphonic acid prevents both the acute locomotor effects of amphetamine and the behavioural sensitization caused by repeated amphetamine injections in rats.

Repeated administration of amphetamine-like psychostimulants produce a progressive and long-lasting hypersensitivity to their behavioural effects known as behavioural sensitization. Previous studies have shown that administration of the purinergic P2 receptor agonist 2-methylthio ATP into the nucleus accumbens of rats raises the extracellular level of dopamine accompanied with enhanced locomotion in a similar manner. Furthermore, the quantitative EEG after application of 2-methylthio ATP or amphetamine was characterized by an elevation of the alpha1-power. However, purinergic P2 receptor antagonists decreased the basal level of dopamine in the NAc and in addition prevented the effects of 2-methylthio ATP. The purpose of the present study was to investigate, whether endogenous ATP acting via purinergic P2 receptors is involved in the process of amphetamine-induced sensitization. Rats were treated systemically for five successive days with d-amphetamine (1.5 mg/kg) and tested in an open field with respect to their locomotor response. The enhanced locomotor activity after the first injection of amphetamine was diminished by the previous intracerebroventricular application of the purinergic P2 receptor antagonist pyridoxalphosphate-6-azophenyl-2'4'-disulphonic acid (PPADS; 0.6 nmol) (P<0.05). The challenge with a lower dose of amphetamine (0.75 mg/kg) produced an increased locomotion in comparison to the response after the first amphetamine application indicating the expression of a behavioural sensitization. Pretreatment with PPADS prior to each amphetamine administration prevented the increase of locomotor activity after the challenge with amphetamine (P<0.05). In summary, the present study demonstrates that PPADS blocks both the acute locomotor effects of amphetamine and the development of behavioural sensitization to the psychostimulant. We suggest that the activation of purinergic P2 receptors by endogenous ATP is necessary for the expression of these effects.

Adenosine Triphosphate↗
PubMed1976

A comparison of dextro-amphetamine and racemic-amphetamine in the treatment of the hyperkinetic syndrome or minimal brain dysfunction.

In a double-blind trial of placebo, dextro-amphetamine, racemic-amphetamine, and methylphenidate, each used for a week, in 48 children with the diagnosis of Minimal Brain Dysfunction or Hyperkinetic Syndrome, it was found that although on the average dextro-amphetamine as well as methylphenidate was significantly superior to racemic-amphetamine, with side effects about the same, in some cases racemic-amphetamine was superior to both dextro-amphetamine and methylphenidate. In 20 cases, improvement was about the same for both the dextro and racemic forms; of these 20, side effects were absent for both in 10 patients; dextro-amphetamine showed fewer side effects in 3 patients, and racemic-amphetamine showed fewer side effects in 7 patients. In 20 other patients, dextro-amphetamine resulted in greater clinical improvement than racemic-amphetamine, while in 7 cases the reverse was true.

Adolescent↗
PubMed2004

A progressive ratio schedule of self-stimulation testing in rats reveals profound augmentation of d-amphetamine reward by food restriction but no effect of a "sensitizing" regimen of d-amphetamine.

RATIONALE: Prior research indicates that psychostimulant-induced sensitization is not expressed in lateral hypothalamic electrical self-stimulation (LHSS)-based measures of drug reward, although the augmenting effect of chronic food restriction is. Neuroadaptations within the brain dopamine system have been identified in both psychostimulant-sensitized and food-restricted animals. Consequently, a variant of the LHSS paradigm in which responding is particularly sensitive to changes in dopaminergic tone may be best suited to detect and compare effects of chronic d-amphetamine and food restriction. Instrumental responding on a progressive ratio (PR) schedule is more sensitive to dopaminergic manipulations than is responding on a continuous reinforcement (CRF) schedule, but has not previously been used to examine chronic psychostimulant and food restriction effects on LHSS-based measures of drug reward. OBJECTIVE: The first aim of this study was to determine whether a regimen of d-amphetamine treatment, that produces locomotor sensitization (5 mg/kg per day x5 days), increases the reward-potentiating effect of d-amphetamine in a PR LHSS protocol. The second aim, was to determine whether chronic food restriction produces a marked increase in the reward-potentiating effect of d-amphetamine in the PR LHSS protocol and, if so, whether it is reversible in parallel with body weight recovery when free feeding is restored. METHOD: Reward-potentiating effects of a challenge dose of d-amphetamine (0.25 mg/kg, IP) were measured in terms of the break point of LHSS responding on a PR schedule of reinforcement, in ad libitum fed and food-restricted rats. RESULTS: A regimen of d-amphetamine treatment that produced locomotor sensitization did not increase the break point for LHSS in the presence or absence of d-amphetamine. Chronic food restriction produced a marked increase in the break point-increasing effect of d-amphetamine (3-fold), which returned to baseline in parallel with body weight recovery over a 4-week period of restored free-feeding. CONCLUSIONS: A locomotor-sensitizing regimen of d-amphetamine treatment does not increase the rewarding effect of LH electrical stimulation or the reward-potentiating effect of d-amphetamine in a PR LHSS protocol. The augmenting effect of chronic food restriction on drug reward is mechanistically and functionally different from psychostimulant sensitization and may be controlled by signals associated with adipose depletion and repletion.

Animals↗
PubMed1988

Effects of chronic amphetamine in BALB/cBy mice, a strain that is not stimulated by acute administration of amphetamine.

The effects of d-amphetamine and methylphenidate on locomotor activity of BALB/cByJ mice were evaluated. d-Amphetamine had no effect or inhibited locomotor activity at acute doses of up to 10 mg/kg while methylphenidate stimulated locomotor activity at acute doses between 10 and 32 mg/kg. The dose-response curves for methylphenidate and d-amphetamine appeared to be quantal in nature. During a 21-day chronic treatment with 10 mg/kg d-amphetamine no evidence of tolerance to the depressant effects of relatively high doses of d-amphetamine was observed. However, a 3.2 mg/kg dose of d-amphetamine, which acutely inhibited locomotor activity, was found to stimulate locomotor activity following chronic amphetamine treatment. Doses of methylphenidate which acutely stimulated activity were without effect in mice chronically receiving amphetamine. Although the mechanism underlying these behavioral effects has yet to be established, our results indicate that inherent alterations can differentially affect both acute and chronic susceptibility to the behavioral effects of amphetamine and methylphenidate. Use of such altered strains of mice can be especially revealing of subtle behavioral effects brought about by chronic drug treatment which are not readily demonstrated following acute administration of amphetamine.

Animals↗
PubMed1980

MDA and DOM: substituted amphetamines that do not produce amphetamine-like discriminative stimuli in the rat.

3,4-Methylenedioxyamphetamine (MDA) and 2,5-dimethoxy-4-methylamphetamine (DOM) are amphetamine congeners that produce both amphetamine-like and LSD-like effects. To evaluate whether MDA and DOM should be classed with amphetamine, their capacity to produce amphetamine-like discriminative stimuli was assessed. Rats were trained to discriminate between saline and 1.0 mg/kg d-amphetamine in a two choice, discrete trial shock avoidance paradigm. Neither MDA nor DOM produced any amphetamine-appropriate responding when tested over a 30-fold dose range. The specificity of the procedure to detect amphetamine-like effects was demonstrated by the failure of LSD to produce any amphetamine-appropriate responding. These results suggest that neither MDA nor DOM should be classed as amphetamine-like agents.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1990

Ontogeny of the enhanced behavioral response to amphetamine in amphetamine-pretreated rats.

Repeated administration of amphetamine to adult rats results in enhanced behavioral responses to subsequent amphetamine exposure. These experiments were designed to determine the earliest age at which behavioral sensitization to amphetamine could be detected. Rats from both sexes (n = 6-8/group) at ages of 1, 7, 21 or 49 postnatal days (PNDs) were injected with either d-amphetamine sulfate (5 mg/kg) or saline, SC, twice daily for 5 consecutive days. Stereotyped behavior and locomotor activity responses to a challenge dose of d-amphetamine (2.5 mg/kg), or saline, IP, were assessed for a total of 90 min, 15 days after the last dose of pretreatment. Amphetamine-induced stereotyped behavior was significantly enhanced only when amphetamine pretreatment was initiated at PND 49, but not at the earlier ages of PND 1, 7 or 21. There was no apparent sex difference in this effect. Correspondingly, amphetamine-induced locomotor activity was reduced in both sexes of the same age group (PND 49), but not in groups pretreated earlier, when compared to the saline-pretreated rats. These results suggest that amphetamine sensitization may be a late-developing effect, one which occurs sometime after the 3rd week of postnatal life.

Aging↗
PubMed1999

Acute fluoxetine treatment potentiates amphetamine hyperactivity and amphetamine-induced nucleus accumbens dopamine release: possible pharmacokinetic interaction.

Amphetamine stimulates locomotor activity, in large part by activating central dopaminergic systems. Serotonin shares on overlapping distribution with dopamine and has been shown to modulate dopaminergic function and dopamine-mediated behaviors. The present study examined whether increasing serotonergic function, via the selective serotonin reuptake inhibitor fluoxetine, would alter the stimulatory effects of amphetamine on locomotor activity and dopamine overflow in the nucleus accumbens. In addition, the present study determined whether fluoxetine treatment would alter the metabolism of amphetamine. Results show that 5.0 mg/kg fluoxetine potentiated the locomotor activity induced by amphetamine (0.5-1.0 mg/ kg), and enhanced the increased dopamine overflow in the nucleus accumbens induced by amphetamine. Fluoxetine treatment also resulted in a higher concentration of amphetamine in the CNS. Together, these findings indicate that acute fluoxetine treatment potentiates the locomotor stimulating and dopamine activating effects of amphetamine. Further, the results indicate that fluoxetine potentiates the effects of amphetamine by decreasing the metabolism of amphetamine, probably through inhibition of cytochrome P450 isozymes.

Adrenergic Uptake Inhibitors↗
PubMed1999

Locomotion and conditioned place preference produced by acute intravenous amphetamine: role of dopamine receptors and individual differences in amphetamine self-administration.

Although previous studies have shown that dopamine (DA) antagonists block amphetamine reward, these studies have utilized animal models that involve repeated exposures to amphetamine. The present investigation examined the effect of DA antagonists on single-trial conditioned place preference (CPP) produced by acute intravenous (i.v.) amphetamine in rats. In the first experiment, rats were prepared with a jugular catheter and then received an acute i.v. injection of amphetamine (0.1-3 mg/kg) paired with one compartment of a CPP apparatus. Relative to sham controls (no i.v. catheter), amphetamine produced a dose-dependent increase in locomotor activity and CPP. Two further experiments demonstrated that both effects of amphetamine were completely blocked by pretreating rats with the D1 DA antagonist SCH-23390 (0.025 and 0.25 mg/kg) or the D2 DA antagonist eticlopride (0.2 and 2 mg/kg) on the conditioning trial. In a final experiment, single-trial amphetamine CPP did not predict subsequent self-administration of i.v. amphetamine (10-50 micrograms/infusion) using either a fixed ratio (FR) 1 or progressive ratio (PR) schedule of reinforcement. Thus, while sharing a similar DA receptor mechanism, the present results indicate that single-trial CPP and self-administration are dissociable effects of i.v. amphetamine.

Amphetamine↗
PubMed2004

Effect of CCK1 and CCK2 receptor blockade on amphetamine-stimulated exploratory behavior and sensitization to amphetamine.

Interactions between dopaminergic neurotransmission and cholecystokinin (CCK) in the CNS may be important in the pathogenesis of psychotic disorders and substance abuse. In this study, the effect of coadministration of the selective CCK receptor antagonists devazepide and L-365,260 (for selectively blocking CCK1 and CCK2 receptors, respectively), on the effect of amphetamine on the rat exploratory behavior, and on sensitization of locomotor response to amphetamine, were studied. Amphetamine (0.5 mg/kg) increased exploratory activity in the exploration box for 5 consecutive testing days, while devazepide (10 microg/kg) blocked and L-365,260 (10 microg/kg) enhanced amphetamine-induced stimulation of activity. Devazepide coadministration prevented the development of sensitization to amphetamine, while coadministration of L-365,260 with amphetamine potentiated the locomotor effect of a challenge dose of amphetamine. These results suggest that endogenous CCK, released during exploratory activity, shapes behavioral responses to amphetamine by acting on both receptor subtypes, and modulates the development of sensitization to amphetamine.

Amphetamine↗
PubMed1998

AMPA-receptors are involved in the expression of amphetamine-induced behavioural sensitisation, but not in the expression of amphetamine-induced conditioned activity in mice.

We investigated the role of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline (NBQX) in the expression of amphetamine-induced behavioural sensitisation and amphetamine-induced conditioned activity in mice. Repeated weekly administration of amphetamine (0.375 mg/kg) for 7 weeks led to an increased locomotor response when challenged with amphetamine 1 week later. NBQX attenuated this increased response at doses (3 and 30 mg/kg) which had no effect on the acute locomotor response to amphetamine. In a separate experiment, mice given amphetamine (1 mg/kg) in a distinctive environment, showed an increased locomotor response within this environment following a subsequent saline administration. NBQX (5-20 mg/kg) had no effect on the expression of this conditioned response. These results suggest that AMPA receptors are involved in the expression of amphetamine-induced behavioural sensitisation in mice, and that this involvement is limited to either the neurobiological effects of amphetamine or the effects of amphetamine on conditioned associations, rather than drug environment conditioned associations.

Amphetamine↗
PubMedDate not supplied

Prenatal amphetamine exposure alters behavioral reactivity to amphetamine in rats.

In utero exposure to psychostimulants produces neurobehavioral alterations in the offspring of laboratory animals. Most amphetamine-related behavioral changes have been related to changes in the monoamine transmission levels, where monoamines may act as developmental regulatory substances for maturation of neuronal population. This study investigates the effect of prenatal-amphetamine exposure on the offspring's behavioral responses under amphetamine conditioning settings. Pregnant female rats were injected (subcutaneous) with amphetamine or saline during the pregnancy [gestation day (GD) 8 until parturition day]. The prenatal amphetamine exposure resulted in significantly decreased birth weights. The offspring from the saline group displayed a significantly lower number of stereotyped behaviors across the four challenge doses of amphetamine injections. Offspring from the amphetamine-treated prenatal group displayed significantly increased average startle amplitude compared to the controlled offspring. Moreover, offspring from amphetamine-treated prenatal group showed significantly less inhibition for the prepulse startle trials compared to those of the offspring from saline group. These results, taken together, indicate that the prenatally exposed rats displayed a significantly different profile of behavioral reactivity upon amphetamine challenges.

Amphetamine↗
PubMed1988

Amphetamine injection into the ventral mesencephalon sensitizes rats to peripheral amphetamine and cocaine.

The daily administration of indirect dopamine agonists, including amphetamine and cocaine, results in a progressive increase in the behavioral stimulant effect of these drugs. Behavioral augmentation also has been shown with opioids such as morphine, and it is known that a stimulant action on dopaminergic perikarya in the ventromedial mesencephalon is critical to the development of behavioral sensitization to morphine. To determine if amphetamine-induced behavioral sensitization might also involve the mesencephalic dopamine neurons, amphetamine was microinjected daily for 2 days into regions of the rat brain containing dopamine cell bodies (A10 and A9 dopamine regions), or dopamine terminals (nucleus accumbens and striatum), and 6 days later amphetamine was given peripherally. It was found that daily amphetamine injection into the A10 or A9 dopamine region, but not into the dopamine terminal fields, significantly potentiated the motor stimulant effect of peripherally administered amphetamine. The behavioral sensitization produced by intracranial injection of amphetamine was found to be dose-dependent. Intra-A10 injection of amphetamine also was found to potentiate the motor stimulant effect of peripheral cocaine. These data indicate that an action by amphetamine in the A10 and A9 dopamine regions may play a critical role in the development of behavioral sensitization.

Amphetamine↗
PubMed2005

Validation of the Cozart Amphetamine Microplate EIA for the analysis of amphetamines in oral fluid.

The purpose of this study was to determine the performance characteristics of the Cozart Amphetamine Microplate EIA for detecting amphetamine in oral fluid. Oral fluid samples were collected using the Cozart RapiScan Collection System from 135 volunteer donors from drug treatment clinics. A further 35 oral fluid samples were collected from volunteer donors who were not drug users. The samples were analyzed in the laboratory using the Cozart Amphetamine Microplate EIA and confirmed using gas chromatography-mass spectrometry (GC-MS). The samples were stored frozen until analysis by GC-MS. The intra-assay precision for the Cozart Amphetamine Microplate EIA for amphetamine in oral fluid over forty assays was 2.74-7.1% CV (within assay) and 3.4-7.0% CV (within day). A total of 78 samples were positive for various amphetamines and related designer drugs. The Cozart Amphetamine Microplate EIA, using a cutoff of 45 ng/ml amphetamine equivalents in neat oral fluid, had a sensitivity of 91.7+/-3.3% and a specificity of 95.9+/-1.9% versus GC-MS using a cutoff of 30 ng/ml. A series of potential adulterants of oral fluid were evaluated and shown not to alter the outcome of the test result.

Amphetamine-Related Disorders↗
PubMed2003

Susceptibility to amphetamine-induced place preference is predicted by locomotor response to novelty and amphetamine in the mouse.

RATIONALE: It has been demonstrated that major differences between mice of the C57BL/6J and DBA/2J inbred strains for amphetamine-induced place conditioning (preference and avoidance, respectively) are evident in standard housing conditions but abolished by temporary restricted feeding. This gene-experience model may be usefully exploited to dissect behavioral phenotypes related to place conditioning induced by addictive drugs. OBJECTIVES: This study evaluated a number of behavioral phenotypes related to amphetamine-induced place preference for strain differences (C57BL/6J vs DBA/2J) susceptible to be abolished by temporary food restriction. METHODS: Mice of the two inbred strains were tested for: (1) conditioned taste aversion and place preference induced by amphetamine within the same dose-range; (2) preference for a novel compartment 24 h after a single exposure to only one of two compartments; (3) amphetamine-induced behavioral sensitization and conditioned hyperactivity; and (4) locomotor activity during exploration of a novel environment. RESULTS: The two strains showed consistent taste aversion at doses of amphetamine that promoted opposite strain-dependent place conditioning. Both strains spent more time exploring the novel rather than the known compartment of the place conditioning apparatus. Instead, only mice of the C57 strain showed amphetamine-induced behavioral sensitization and conditioned hyperactivity. However, temporary food restriction did not affect strain differences for these phenotypes. Finally, C57 mice were more active than DBA in a novel environment and restricted feeding abolished this strain-dependent difference. CONCLUSIONS: These results relate individual differences for amphetamine-induced place conditioning with locomotor response to amphetamine and novelty.

Amphetamine↗
PubMed2006

Amphetamine-induced locomotion, behavioral sensitization to amphetamine, and striatal D2 receptor function in rats with high or low spontaneous exploratory activity: differences in the role of locus coeruleus.

Individual differences in novelty-related behavior are associated with sensitivity to various neurochemical manipulations. In the present study the amphetamine-induced locomotor activity and behavioral sensitization to amphetamine (0.5 mg/kg) was investigated in rats with high or low spontaneous exploratory activity (HE- and LE-rats, respectively) after partial denervation of the locus coeruleus (LC) projections with a low dose of the selective neurotoxin DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine; 10 mg/kg). DSP-4 produced a partial depletion (about 30%) of noradrenaline in the frontal cortex of both HE- and LE-rats; additionally the levels of metabolites of dopamine and 5-HT were reduced in the frontal cortex and nucleus accumbens of the LE-rats. Amphetamine-stimulated locomotor activity was attenuated by the DSP-4 pretreatment only in the HE-rats and this effect persisted over repeated testing. Behavioral sensitization to repeated amphetamine was evident only in the LE-rats with intact LC projections. Repeated amphetamine treatment reduced D(2) receptor mediated stimulation of [(35)S]GTPgammaS-binding and dopamine-dependent change in GDP-binding affinity in the striatum, but only in HE-rats. The absence of amphetamine sensitization in HE-rats could thus be related to the downregulation by amphetamine of the G protein stimulation through D(2) receptors. Conclusively, acute and sensitized effects of amphetamine depend on the integrity of LC projections but are differently regulated in animals with high or low trait of exploratory activity. These findings have implications to the neurobiology of depression, drug addiction, and attention deficit hyperactivity disorder.

Amphetamine↗
PubMed2003

D(3) dopamine receptors are down-regulated in amphetamine sensitized rats and their putative antagonists modulate the locomotor sensitization to amphetamine.

D(3) dopamine receptor agonists inhibit locomotor activity in rodents and modulate the reinforcing effect of psychostimulants; however, their functional role during behavioral sensitization remains unclear. In the present study, we intend to investigate if D(3) dopamine receptors alter during the amphetamine sensitization and test if manipulation of D(3) receptors would affect the development of locomotor sensitization to amphetamine. We have found that D(3) dopamine receptors are down-regulated in the limbic forebrain in chronic amphetamine-treated (5 mg/kg x 7 days) animals. The levels of both D(3) receptor protein (B(max) value) and mRNA decreased significantly in the behaviorally sensitized rats compared to the saline-treated controls. When animals were co-administered a putative D(3) receptor antagonist (U99194A or GR103691; 20 microg x 7 days; intracerebroventricle) and amphetamine (5 mg/kg x 7 days, i.p.), the locomotor sensitization to amphetamine was significantly inhibited. However, when the putative D(3) receptor antagonist U99194A was administered during the amphetamine withdrawal period at day 10, it did not affect the development of locomotor sensitization. Furthermore, pretreatment with the preferential D(3) agonist 7-hydroxydipropylaminotetralin partially blocked the inhibitory effect of U99194A on locomotor sensitization. These data prove the participation of D(3) dopamine receptors in the development of amphetamine sensitization and, in addition, suggest a potential application for D(3) antagonists in the prevention of amphetamine addiction.

Amphetamine↗
PubMedDate not supplied

Fluorescence polarization immunoassay detection of amphetamine, methamphetamine, and illicit amphetamine analogues.

The Abbott Diagnostics Amphetamine/Methamphetamine II and Amphetamine Class reagents were evaluated on the Abbott TDx for cross-reactivity to amphetamine and methamphetamine stereoisomers, several of their metabolites, and various illicit analogues, including 2-methoxyamphetamine, 4-hydroxymethamphetamine, 2,5-dimethoxy-amphetamine (DMA), 4-bromo-2,5-dimethoxyamphetamine (DOB), 4-bromo-2,5-dimethoxy-beta-phenethylamine (BDMPEA), 3,4,5-trimethoxyamphetamine (TMA), 3,4-methylenedioxy-amphetamine (MDA) N,N-dimethyl-3,4-methylenedioxy-amphetamine, N-hydroxy-3,4-methylenedioxyamphetamine (N-OH MDA), 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyethylamphetamine (MDEA), 2,5-dimethoxy-4-ethylamphetamine (DOE), 2,5-dimethoxy-4-methylamphetamine (DOM), and mescaline in concentrations ranging from 100 to 100,000 ng/mL. Results demonstrate the utility of this assay for detection of several of the above compounds; unfortunately many are still not detectable. Significant differences were observed between the Amphetamine/Methamphetamine II and Amphetamine Class reagents, particularly regarding their cross-reactivity to over-the-counter medications. Detection of the drugs amphetamine, methamphetamine, and the illicit analogues is not enhanced with the Amphetamine Class reagents, and unless detection of the over-the-counter compounds is of interest, these reagents are a poor choice compared to the Amphetamine/Methamphetamine II reagents. Cross-reactivity of some of the illicit analogues is such that the assay can reliably be used for the routine screening of these compounds.

Amphetamines↗