Gamma-aminobutyric acid-sub(A) agonists differentially gnawing induced by indirect-acting dopamine agonists in C57BL/6J mice

Evaluated the interaction of either gaboxadol HCl (THIP) or muscimol, both gamma-aminobutyric acid (GABA) type A agonists, with indirect-acting dopamine agonists (DAGs) methylphenidate, (+)-amphetamine, metamphetamine, amfonelic acid, indatraline, nomifensine, diclofensine, mazindol, and GBR 12935 and with direct-acting DAGs WIN 35,428, bupropion, GBR 12909, and cocaine. 1,832 male C57BL/6J mice were given either with saline or 1 of the doses of THIP or muscimol before an injection of a dopamine agonist. Gnawing on corrugated packing paper was measured. Results showed that: (1) indirect- but not direct-acting DAGs induced gnawing, (2) gnawing induced by indirect-acting DAGs GBR 12935, nomifensine and mazindol was potentiated in mice in which GABA type A receptors were stimulated either by THIP or muscimol, and (3) indirect DAGs had a differential sensitivity to the effects of THIP and muscimol. ((c) 1998 APA/PsycINFO, all rights reserved

Pharmacotherapy of methamphetamine addiction: an update

Abstract Methamphetamine dependence is a serious public health problem worldwide for which there are no approved pharmacological treatments. Psychotherapy is still the mainstay of treatment; however, relapse rates are high. The search for effective pharmacological treatment has intensified in the last decade. This review will highlight progress in pharmacological interventions to treat methamphetamine dependence as well as explore new pharmacological targets. Published data from clinical trials for stimulant addiction were searched using PubMed and summarized, as well as highlights from a recent symposium on methamphetamine pharmacotherapy presented at the ISAM 2006 meeting, including interim analysis data from an ongoing D-amphetamine study in Australia. Early pilot data are encouraging for administering D-amphetamine and methylphenidate as treatment for heavy amphetamine users. Abilify at 15 mg/day dose increased amphetamine use in an outpatient pilot study. Sertraline, ondansetron, baclofen, tyrosine, and imipramine were ineffective in proof-of-concept studies. Development of pharmacotherapy for methamphetamine dependence is still in an early stage. Data suggesting D-amphetamine and methylphenidate as effective pharmacotherapy for methamphetamine addiction will need to be confirmed by larger trials. Preclinical data suggest that use of GVG, CB1 antagonist, and lobeline are also promising therapeutic strategies.Ahmed Elkashef, Frank Vocci, Glen Hanson, Jason White, Wendy Wickes and Jari Tiihone