Dataset Information

Amphetamine, but not methylphenidate, increases ethanol intake in adolescent male, but not in female, rats.

ABSTRACT: Introduction:There has been an increasing interest in analyzing the interactions between stimulants and ethanol during childhood and adolescence. Stimulants are used to treat attention-deficit hyperactivity disorder (ADHD) in these developmental stages, during which ethanol initiation and escalation often occur. Methods:This study assessed the effects of repeated d-amphetamine (AMPH) or methylphenidate (MPH) treatment during adolescence [male and female Wistar rats, between postnatal day (PD) 28 to PD34, approximately] on the initiation of ethanol intake during a later section of adolescence (PD35 to PD40). Results:Amphetamine and MPH exerted reliable acute motor stimulant effects, but there was no indication of sensitized motor or anxiety responses. MPH did not affect dopamine (DA) levels, whereas AMPH significantly reduced insular levels of DA in both sexes and norepinephrine levels in females only. Repeated treatment with AMPH, but not with MPH, enhanced ethanol intake during late adolescence in male, but not in female, rats. Conclusion:A short treatment with AMPH during adolescence significantly altered DA levels in the insula, both in male and females, and significantly enhanced ethanol intake in males. The present results suggest that, in adolescent males, a very brief history of AMPH exposure can facilitate the initiation of ethanol intake.

SUBMITTER: Ruiz P

PROVIDER: S-EPMC5893334 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Amphetamine, but not methylphenidate, increases ethanol intake in adolescent male, but not in female, rats.

Ruiz Paul P Calliari Aldo A Genovese Patricia P Scorza Cecilia C Pautassi Ricardo Marcos RM

Brain and behavior 20180219 4

<h4>Introduction</h4>There has been an increasing interest in analyzing the interactions between stimulants and ethanol during childhood and adolescence. Stimulants are used to treat attention-deficit hyperactivity disorder (ADHD) in these developmental stages, during which ethanol initiation and escalation often occur.<h4>Methods</h4>This study assessed the effects of repeated d-amphetamine (AMPH) or methylphenidate (MPH) treatment during adolescence [male and female Wistar rats, between postna ...[more]

PMID: 29670821

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Project description:Adolescent psychostimulant abuse has been on the rise over the past decade. This trend has demonstrable ramifications on adolescent behavior and brain morphology, increasing risk for development of addiction during adolescence and in later adulthood. Neuroimmune substrates are implicated in the etiology of substance use disorders. To add to this body of work, the current study was developed to explore the role of a chemokine receptor, CXC Chemokine Receptor 4 (CXCR4), in the development of amphetamine (AMPH) sensitization. We targeted CXCR4 as it is implicated in developmental processes, dopaminergic transmission, neuroimmune responses, and the potentiation of psychostimulant abuse pathology. To evaluate the role of CXCR4 activity on the development of AMPH sensitization, a CXCR4 antagonist (Plerixafor; AMD3100) was administered to rats as a pretreatment variable. Specifically, adolescent Long Evans male rats (N = 37) were divided into four groups: (1) AMD3100 (IP, 4.0 mg/kg) + AMPH (IP, 4.0 mg/kg), (2) saline (SAL; 0.9% NaCl) + AMPH, (3) AMD3100 + SAL, and (4) SAL + SAL. Animals were first habituated to locomotor activity (LMA) chambers, then injected with a pretreatment drug (AMD3100 or SAL) followed by AMPH or SAL every other for four days. After a one-week withdrawal period, all animals were administered a low challenge dose of AMPH (IP, 1.0 mg/kg). AMPH-injected rats displayed significantly more locomotor activity compared to controls across all testing days. CXCR4 antagonism significantly attenuated AMPH-induced locomotor activity. On challenge day, AMD3100 pre-treated animals exhibited diminutive AMPH-induced locomotor activity compared to SAL pre-treated animals. Postmortem analyses of brain tissue revealed elevated CXCR4 protein levels in the striatum of all experimental groups. Our results implicate CXCR4 signaling in the development of AMPH sensitization and may represent an important therapeutic target for future research in psychostimulant abuse.

Project description:Epidemiological studies suggest that binge drinking is prevalent among adolescents, and may result in neurobehavioral consequences. Animal models provide the experimental control to investigate the consequences of "binge" alcohol exposure during this neurodevelopmental epoch. The current study used an animal model that combined an intermittent pattern of alcohol vapor exposure with voluntary drinking of 20% unsweetened alcohol in adolescent male and female Wistar rats (postnatal day [PD] 22-62), in order to test for potential differences in behavioral changes, ethanol drinking, and hypocretin/orexin (Hcrt/OX) signaling associated with exposure status. Two weeks after discontinuation of the alcohol vapor exposure and drinking during adolescence, rats were tested in adulthood for anxiety-like behaviors using a modified open-field conflict task, pre-pulse facilitation of startle response, light/dark box, and marble burying test. Adolescent alcohol exposure led to overall decreased startle response and increased behavioral arousal in the light/dark chamber during adulthood. Additionally, male rats demonstrated more disinhibited behavior during the conflict task compared to females, and female rats exhibited more rearing behavior during the light/dark test. Rats were also given a 2-bottle choice test that resulted in adolescent alcohol-exposed rats drinking significantly more alcohol in adulthood. Further, female rats also consumed more alcohol in adulthood compared to males. Estrous cycle phase did not account for any of the sex differences observed in the behavioral measures. Histological results indicated that adolescent alcohol did not alter Hcrt/OX-1 or Hcrt/OX-2 receptor mRNA expression levels in adult rats compared to control adults. However, female rats expressed a higher level of Hcrt/OX-1 and Hcrt/OX-2 receptor mRNA in the frontal cortex compared to males. These data suggest that our current model of intermittent ethanol exposure in adolescence can modestly affect both behavior and future consumption of alcohol and that Hcrt/OX receptor signaling differs between males and females.

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Dataset Information

Amphetamine, but not methylphenidate, increases ethanol intake in adolescent male, but not in female, rats.

Publications

Amphetamine, but not methylphenidate, increases ethanol intake in adolescent male, but not in female, rats.

Similar Datasets

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