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Differential effects of chronic amphetamine and baclofen administration on cAMP levels and phosphorylation of CREB in distinct brain regions of wild type and monoamine oxidase B‐deficient mice
Author(s) -
Yin HsiangShu,
Chen Kevin,
Kalpana Sriram,
Shih Jean C.
Publication year - 2006
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20334
Subject(s) - baclofen , creb , amphetamine , olfactory bulb , endocrinology , striatum , dopaminergic , chemistry , gabab receptor , agonist , medicine , pharmacology , dopamine , central nervous system , receptor , biochemistry , transcription factor , gene
Roles of GABA B transmission were explored in the action of amphetamine (Amph) on the brain. Adult male wild type (WT) and monoamine oxidase B‐knocked out (MAOBKO) mice received i.p. injections of saline, d‐Amph (5 mg/kg), plus baclofen (GABA B receptor agonist, 10 mg/kg), or baclofen and Amph, twice daily for 3 days and single treatments on day 4, followed by immuno‐cyclic‐AMP (cAMP) and immunoblotting assays on the brain tissue. The WT mice responded with higher levels of behavioral responses than the KO to the daily Amph injection; however, baclofen blocked the Amph‐induced behavioral hyperactivity of both WT and KO mice. After the last treatment, levels of cAMP and phosphorylated (p) cyclic‐AMP response element binding protein (CREB) were up‐regulated in the striatum and somatosensory cortex of Amph‐treated WT mice, while similar to the saline‐controls in the baclofen+Amph‐treated group, indicating the blockade by baclofen to Amph. Baclofen similarly suppressed the Amph‐induced increases in pCREB levels of WT hippocampus and amygdala, and decreases of olfactory bulb and thalamus. For MAOBKO mice, baclofen hindered the Amph‐generated increases in motor cortical cAMP and pCREB, and amygdaloid pCREB, and the decrease in olfactory bulb pCREB, whereas did not affect the Amph‐raised hippocampal pCREB. Furthermore, the levels of CREB were variably modified in distinct regions by the drug exposures. The data reveal that the GABA B ‐mediated intracellular signaling differentially participates in mechanisms underlying Amph perturbation to various regions, and may thereby contribute explanations to the behavioral consequences. Moreover, MAOB is region‐dependently involved in responses of the brain to Amph and baclofen, supporting interactions between GABA and monoamines. Synapse 60:573–584, 2006. © 2006 Wiley‐Liss, Inc.