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Fenobam sulfate inhibits cocaine-taking and cocaine-seeking behavior in rats: implications for addiction treatment in humans
Psychopharmacology (2013)
  • Dr. Thomas M. Keck, Rowan University
  • Hong-Ju Yang
  • Guo-Hua Bi
  • Yong Huang
  • Hai-Ying Zhang
  • Ratika Srivastava
  • Eliot L. Gardner
  • Amy Hauck Newman
  • Zheng-Xiong Xi
Abstract
Rationale
The metabotropic glutamate receptor subtype 5 (mGluR5) has been reported to be critically involved in drug reward and addiction. Because the mGluR5 negative allosteric modulators (NAMs) 2-methyl-6-(phenylethynyl)pyridine (MPEP) and 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine (MTEP) significantly inhibit addictivelike behaviors of cocaine and other drugs of abuse in experimental animals, it has been suggested that mGluR5 NAMs may have translational potential for treatment of addiction in humans. However, neither MPEP nor MTEP have been evaluated in humans due to their off-target actions and rapid metabolism.

Objectives
Herein, we evaluate a potential candidate for translational addiction research: a new sulfate salt formulation of fenobam, a selective mGluR5 NAM that has been investigated in humans.

Results
In rats, fenobam sulfate had superior pharmacokinetics compared to the free base, with improved maximal plasma concentration (Cmax) and longer half life. Oral (p.o.) administration of fenobam sulfate (30 or 60 mg/kg) inhibited intravenous (i.v.) cocaine self-administration, cocaine-induced reinstatement of drug-seeking behavior, and cocaine-associated cue-induced cocaine-seeking behavior in rats. Fenobam sulfate also inhibited p.o. sucrose self-administration and sucrose-induced reinstatement of sucrose-seeking behavior, but had no effect on locomotion.

Conclusions
This study provides additional support for the role of mGluR5 signaling in cocaine addiction and suggests that fenobam sulfate may have translational potential in medication development for the treatment of cocaine addiction in humans.
Keywords
  • Cocaine,
  • Fenobam,
  • Self-administration,
  • Reinstatement,
  • Cocaine-seeking behavior,
  • Incubation of cocaine craving,
  • mGluR5
Disciplines
Publication Date
September, 2013
DOI
10.1007/s00213-013-3106-9
Citation Information
Thomas M. Keck, Hong-Ju Yang, Guo-Hua Bi, Yong Huang, et al.. "Fenobam sulfate inhibits cocaine-taking and cocaine-seeking behavior in rats: implications for addiction treatment in humans" Psychopharmacology Vol. 229 Iss. 2 (2013) p. 253 - 265 ISSN: 0033-3158
Available at: http://works.bepress.com/thomas-keck/4/