Neurochemical Research

, Volume 41, Issue 12, pp 3206–3214 | Cite as

The Nicotinic α6-Subunit Selective Antagonist bPiDI Reduces Alcohol Self-Administration in Alcohol-Preferring Rats

  • Jirawoot Srisontiyakul
  • Hanna E. Kastman
  • Elena V. Krstew
  • Piyarat Govitrapong
  • Andrew J. Lawrence
Original Paper

Abstract

Cigarettes and alcohol are the most abused substances in the world and are commonly co-abused. Nicotine primarily acts in the brain on nicotinic acetylcholine receptors (nAChR), which are also a target for alcohol. The alpha6 subunit of nAChR is expressed almost exclusively in the brain reward system and may modulate the rewarding properties of alcohol and nicotine. Recently, N,N-decane-1,10-diyl-bis-3-picolinium diiodide (bPiDI) was synthesized as a selective, brain penetrant α6 subunit antagonist that reduces nicotine self-administration. The current study aimed to examine the effects of bPiDI on alcohol self-administration in inbred alcohol-preferring (iP) rats. Adult, male iP rats were trained to self-administer alcohol or sucrose. Once stable responding was achieved, rats were injected with bPiDI (1, 3 mg/kg, i.p.) and tested for self-administration under fixed and progressive ratio schedules of reinforcement. They subsequently underwent extinction, in which no rewards or cues were presented in the operant chambers. Then, they were injected with bPiDI prior to testing for cue-induced reinstatement of reward seeking. bPiDI (3 mg/kg) significantly reduced alcohol self-administration in both fixed and progressive ratios without any effects on sucrose self-administration or locomotor activity. In contrast, bPiDI (3 mg/kg) did not inhibit cue-induced reinstatement of either alcohol or sucrose seeking. The results support the involvement of α6 containing nAChR in reinforcing effects of alcohol, but not relapse to alcohol-seeking, without any impact on responding for a natural reward or general activity. bPiDI may be a potential lead molecule for a therapeutic strategy to limit nicotine and alcohol consumption.

Keywords

Alpha6 Nicotinic Acetylcholine receptor bPiDI Alcohol Self administration 

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Jirawoot Srisontiyakul
    • 1
  • Hanna E. Kastman
    • 2
  • Elena V. Krstew
    • 2
  • Piyarat Govitrapong
    • 1
    • 3
  • Andrew J. Lawrence
    • 2
    • 4
  1. 1.Research Center for Neuroscience, Institute of Molecular BiosciencesMahidol UniversitySalayaThailand
  2. 2.Florey Institute of Neuroscience and Mental HealthUniversity of MelbourneParkvilleAustralia
  3. 3.Center for Neuroscience and Department of Pharmacology, Faculty of ScienceMahidol UniversityBangkokThailand
  4. 4.Florey Department of NeuroscienceUniversity of MelbourneParkvilleAustralia

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