Chronic haloperidol alters dopamine receptors: effects of cocaine exposure during the preweaning period

The translational value of preclinical models of methamphetamine abuse depends in large part on the degree to which the drug regimens used in animals produce methamphetamine exposure patterns similar to those experienced by human methamphetamine abusers. To approximate one common form of methamphetamine abuse, we studied the effects of a schedule of intravenous methamphetamine administration in rats which included 2 weeks of progressively more frequent drug injections (0.125 mg/kg/injection) followed by 40 maintenance days during which animals received 40 daily injections (at 15-min intervals), with the dose gradually increasing (0.125-0.25 mg/kg per injection) every 5-10 days. This treatment produced an emerging behavioral profile characterized by gradually more continuous periods of activation consisting of progressively more intense, focused stereotypy interrupted by episodic bursts of locomotion. We also assessed markers of dopamine neurotransmission (dopamine transporter, vesicular monoamine transporter, and dopamine D1 and D2 receptors) at 15 min and (including dopamine levels) at 6 and 30 days following cessation of methamphetamine treatment. All dopamine components measured in caudate-putamen were significantly reduced at 15 min and 6 days after the final methamphetamine injection. Dopamine D1 and D2 receptors fully recovered after 30 days of drug abstinence, whereas dopamine and the dopamine transporter exhibited significant but incomplete recovery by this time point. In contrast, only the vesicular monoamine transporter exhibited no evidence of recovery over the 30-day withdrawal period. These data are discussed in terms of damage to dopamine terminals and compensatory adjustments in mechanisms maintaining functional dopaminergic transmission.

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Prolonged exposure of rats to intravenous methamphetamine: behavioral and neurochemical characterization

Segal

Kuczenski

O'Neil

et al. 2005

Psychopharmacology

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An animal model with relevance to schizophrenia: sex-dependent cognitive deficits in osteogenic disorder-Shionogi rats induced by glutathione synthesis and dopamine uptake inhibition during development

Castagné

Cuénod

2004

Neuroscience

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Blunted metabolic response to SKF 82958 in the mesolimbic system following preweaning cocaine treatment

Melnick

Dow-Edwards

2003

Developmental Brain Research

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Chronic haloperidol alters dopamine receptors: effects of cocaine exposure during the preweaning period

Cited by 4 publications

References 37 publications

Prolonged exposure of rats to intravenous methamphetamine: behavioral and neurochemical characterization

Prolonged exposure of rats to intravenous methamphetamine: behavioral and neurochemical characterization

An animal model with relevance to schizophrenia: sex-dependent cognitive deficits in osteogenic disorder-Shionogi rats induced by glutathione synthesis and dopamine uptake inhibition during development

Blunted metabolic response to SKF 82958 in the mesolimbic system following preweaning cocaine treatment

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