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COCAINE‐INDUCED ALTERATIONS IN D2/D3 RECEPTOR FUNCTION IN MALE RATS WITH AND WITHOUT TESTOSTERONE REPLACEMENT
Author(s) -
MenéndezDelmestre Raissa,
Segarra Annabell C
Publication year - 2006
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.20.4.a382
Subject(s) - testosterone (patch) , testosterone replacement , medicine , endocrinology , function (biology) , receptor , chemistry , biology , androgen , microbiology and biotechnology , hormone
Previous studies in our laboratory indicate that testosterone modulates cocaine‐induced locomotor activity in the male rat. In this study, functional autoradiography was used to investigate cocaine modulation of D 2 /D 3 receptors in male rats. Adult Sprague‐Dawley rats were orchidectomized and received an empty (GDX) or testosterone‐filled (GDX‐T) silastic implant. A week later, they received a daily injection of saline or cocaine (15 mg/kg,i.p.) for 5 days. On day 13 they received another cocaine injection (15 mg/kg, i.p.). To determine D 2 /D 3 receptor function, quinpirole‐stimulated [ 35 S] GTPγ S binding was assessed in the striatum (STR) and nucleus accumbens (NAc). GDX males showed higher levels of D 2 /D 3 signal transduction in the STR and NAc compared to GDX‐T males. When rats were injected with cocaine, we observed that only GDX‐T males showed an increase in quinpirole‐stimulated [ 35 S] GTPγ S binding in these brain areas. The cocaine paradigm for our studies did not induce behavioral sensitization in GDX‐T males but it did in GDX males, which did not show robust changes in D 2 /D 3 function in the brain areas studied. These data indicate that D 2 /D 3 function is modulated by testosterone in male rats and suggest an inhibitory role of D 2 /D 3 in behavioral sensitization. This work was supported partially by NIH grants U54 NS3905 04 (NINDS/SNRP); SO6‐GM08224 (MBRS/SCORE), RR03051 (NCRR/RCMI); and R25 GM61838 (MBRS/RISE)