title: Glial cell modulators attenuate methamphetamine self-administration in the rat.
abstract: Neuroinflammation induced by activated microglia and astrocytes can be elicited by drugs of abuse. Methamphetamine administration activates glial cells and increases proinflammatory cytokine production, and there is recent evidence of a linkage between glial cell activation and drug abuse-related behavior. We have previously reported that ibudilast (AV411; 3-isobutyryl-2-isopropylpyrazolo-[1,5-a]pyridine), which inhibits phosphodiesterase (PDE) and pro-inflammatory activity, blocks reinstatement of methamphetamine-maintained responding in rats, and that ibudilast and AV1013, an amino analog of ibudilast, which has similar glial-attenuating properties but limited PDE activity, attenuate methamphetamine-induced locomotor activity and sensitization in mice. The present study's objective was to determine whether co-administered ibudilast, AV1013, or minocycline, which is a tetracycline derivative that also suppresses methamphetamine-induced glial activation, would attenuate active methamphetamine i.v. self-administration in Long-Evans hooded rats. Rats were initially trained to press a lever for 0.1mg/kg/inf methamphetamine according to a FR1 schedule during 2-h daily sessions. Once stable responding was obtained, twice daily ibudilast (1, 7.5, 10mg/kg), AV1013 (1, 10, 30mg/kg), or once daily minocycline (10, 30, 60mg/kg), or their corresponding vehicles, were given i.p. for three consecutive days during methamphetamine (0.001, 0.03, 0.1mg/kg/inf) self-administration. Ibudilast, AV1013, and minocycline all significantly (p<0.05) reduced responding maintained by 0.03mg/kg/inf methamphetamine that had maintained the highest level of infusions under vehicle conditions. These results suggest that targeting glial cells may provide a novel approach to pharmacotherapy for treating methamphetamineabuse.
authors: Department of Pharmacology & Toxicology, Virginia Commonwealth University, Richmond, VA 23298-0613, USA.
authors: Sarah E
authors: SE
authors: Snider
authors: Elizabeth S
authors: ES
authors: Hendrick
authors: Patrick M
authors: PM
authors: Beardsley
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage*; D008911:Minocycline / Q000494:pharmacology; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D012646:Self Administration; D019966:Substance-Related Disorders / Q000473:pathology / Q000517:prevention & control; D007212:Indolizines; D011720:Pyrazoles
chemical_list: D008694:Methamphetamine; D008911:Minocycline; D011725:Pyridines; C573066:AV1013; C038366:ibudilast; D007212:Indolizines; D011720:Pyrazoles
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