Premium
SN79, A Novel Sigma (σ) ‐ 2 Receptor Antagonist, Attenuates Cocaine‐Induced Behaviors In Mice
Author(s) -
Kaushal Nidhi,
Croom Caroline,
Shaikh Jamaluddin,
Narayanan Sanju,
Mesangeau Christophe,
Poupaert Jacques H,
McCurdy Christopher R,
Matsumoto Rae R
Publication year - 2008
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.22.1_supplement.713.15
Subject(s) - receptor , radioligand , pharmacology , stimulant , antagonist , drugs of abuse , sigma receptor , addiction , cocaine abuse , sigma 1 receptor , chemistry , drug , medicine , agonist , psychiatry
Cocaine is highly addictive and its abuse is involved in more emergency room visits than any other illicit drug. Unfortunately, there is no effective pharmacotherapy to treat it. Cocaine interacts with both sigma (σ)‐1 & 2 receptors. The role of σ‐1 receptors in attenuating cocaine‐induced behaviors has been established using pharmacological antagonists and antisense oligonucleotides. In contrast, the role of σ‐2 receptors in the treatment of cocaine abuse is unclear due to the lack of σ‐2 selective compounds. In the present study, radioligand and behavioral studies were conducted to characterize SN79, a putative σ‐2 selective compound. Radioligand binding studies showed that SN79 has nanomolar affinity for σ‐2 receptors and negligible affinity for σ‐1 receptors. In behavioral studies, pretreatment of male, Swiss Webster mice with SN79 (0.1–10 mg/kg) significantly attenuated the effects produced by a convulsive (70 mg/kg) or locomotor stimulant (20 mg/kg) dose of cocaine. SN79 also significantly blocked the development and expression of the sensitized response to subchronic treatment with cocaine. Alone, SN79 had sedative effects at acute higher doses, which disappeared upon repeated exposure. These results point towards the importance of targeting σ‐2 receptors in the development of an effective anti‐cocaine therapy, and also establish SN79 as the most σ‐2 selective compound to date. (Support: DA013978 , DA023205 )