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The Non‐Preganglionic Edinger‐Westphal Nucleus is differentially responsive to psychostimulants
Author(s) -
Datta Ronjon Kumar,
Cote Dawn M,
Voorhees Charlene M,
Ryabinin Andrey E
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a598-c
Subject(s) - methamphetamine , nucleus accumbens , conditioned place preference , nucleus , pharmacology , ethanol , chemistry , c fos , brain stimulation reward , immunohistochemistry , medicine , addiction , neuroscience , endocrinology , biology , central nervous system , gene expression , biochemistry , gene
In order to alleviate the problem of drug addiction, it is essential to identify the neurobiological substrates that regulate the behavioral effects of these drugs. Inducible transcription factors, such as c‐FOS, are reliable markers for neuronal activity, which reveal brain regions affected by a particular drug. It has been shown that the non‐preganglionic Edinger‐Westphal nucleus (npEW), the main source of urocortin (Ucn) in the brain, is preferentially sensitive to ethanol. Animals with higher levels of Ucn in npEW show greater preference for ethanol and lesions of this nucleus block ethanol preference, indicating that npEW is involved in regulation of alcohol intake. The current study compared the response of npEW neurons to interperitoneal injections of ethanol (2.5 g/kg), cocaine (30 mg/kg), and methamphetamine (10 mg/kg) in male C57BL/6J mice. The immunohistochemical analysis shows that cocaine and ethanol, but not methamphetamine, induce c‐FOS in npEW. Double‐immunohistochemistry confirmed that c‐FOS induction occurred in Ucn‐containing neurons. The lack of npEW response to methamphetamine was not due to insufficient dose because other brain regions (the VTA and nucleus accumbens) were more responsive to this drug than cocaine or ethanol. These results point to npEW as a target of drug action, and potentially a critical region for drug addiction. Support: NIH grants AA013738 and AA016647