Nicotine Modulates Alcohol-Seeking and Relapse by Alcohol-Preferring (P) Rats in a Time-Dependent Manner

Sheketha R. Hauser, Bruk Getachew, Scott M. Oster, Ronnie Dhaher, Zheng Ming Ding, Richard L. Bell, William J. Mcbride, Zachary A. Rodd

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Background: Alcohol is frequently co-abused with smoking. In humans, nicotine use can increase alcohol craving and consumption. The objectives of the current study were to assess the acute effects of nicotine on alcohol seeking and relapse at 2 different time points. Methods: Adult female alcohol-preferring (P) rats were trained in 2-lever operant chambers to self-administer 15% ethanol (EtOH) (v/v) and water on a concurrent fixed-ratio 5-fixed-ratio 1 (FR5-FR1) schedule of reinforcement in daily 1-hour sessions. Following 10weeks of daily 1-hour sessions, rats underwent 7 extinction sessions, followed by 2weeks in their home cages. Rats were then returned to the operant chambers without EtOH or water being present for 4 sessions (Pavlovian Spontaneous Recovery [PSR]). Rats were then given a week in their home cage before being returned to the operant chambers with access to EtOH and water (relapse). Nicotine (0, 0.1, 0.3, or 1.0mg/kg) was injected subcutaneously immediately or 4hours prior to PSR or relapse testing. Results: Injections of nicotine immediately prior to testing reduced (5 to 10 responses PSR; 50 to 60 responses relapse), whereas injections of nicotine 4hours prior to testing increased (up to 150 responses for PSR; up to 400 responses for relapse with 1.0mg/kg dose) responses on the EtOH lever during PSR and relapse tests. Conclusions: The results of this study demonstrate that acute effects of nicotine on EtOH-seeking and relapse behaviors may be time dependent, with the immediate effects being a result of nicotine possibly acting as a substitute for EtOH, whereas with a delay of 4hours, priming effects of nicotine alterations in nicotinic receptors, and/or the effects of nicotine's metabolites (i.e., cotinine and nornicotine) may enhance the expression of EtOH-seeking and relapse behaviors.

Original languageEnglish (US)
Pages (from-to)43-54
Number of pages12
JournalAlcoholism: Clinical and Experimental Research
Volume36
Issue number1
DOIs
StatePublished - Jan 1 2012

Fingerprint

Nicotine
Rats
Alcohols
Recurrence
Recovery
nornicotine
Water
Testing
Reinforcement Schedule
Cotinine
Injections
Nicotinic Receptors
Metabolites
Alcohol Drinking
Reinforcement
Ethanol
Smoking

Keywords

  • Alcohol-Preferring Rat
  • Ethanol Relapse
  • Ethanol-Seeking
  • Nicotine
  • Pavlovian Spontaneous Recovery

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Psychiatry and Mental health
  • Toxicology

Cite this

Nicotine Modulates Alcohol-Seeking and Relapse by Alcohol-Preferring (P) Rats in a Time-Dependent Manner. / Hauser, Sheketha R.; Getachew, Bruk; Oster, Scott M.; Dhaher, Ronnie; Ding, Zheng Ming; Bell, Richard L.; Mcbride, William J.; Rodd, Zachary A.

In: Alcoholism: Clinical and Experimental Research, Vol. 36, No. 1, 01.01.2012, p. 43-54.

Research output: Contribution to journalArticle

Hauser, Sheketha R. ; Getachew, Bruk ; Oster, Scott M. ; Dhaher, Ronnie ; Ding, Zheng Ming ; Bell, Richard L. ; Mcbride, William J. ; Rodd, Zachary A. / Nicotine Modulates Alcohol-Seeking and Relapse by Alcohol-Preferring (P) Rats in a Time-Dependent Manner. In: Alcoholism: Clinical and Experimental Research. 2012 ; Vol. 36, No. 1. pp. 43-54.
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abstract = "Background: Alcohol is frequently co-abused with smoking. In humans, nicotine use can increase alcohol craving and consumption. The objectives of the current study were to assess the acute effects of nicotine on alcohol seeking and relapse at 2 different time points. Methods: Adult female alcohol-preferring (P) rats were trained in 2-lever operant chambers to self-administer 15{\%} ethanol (EtOH) (v/v) and water on a concurrent fixed-ratio 5-fixed-ratio 1 (FR5-FR1) schedule of reinforcement in daily 1-hour sessions. Following 10weeks of daily 1-hour sessions, rats underwent 7 extinction sessions, followed by 2weeks in their home cages. Rats were then returned to the operant chambers without EtOH or water being present for 4 sessions (Pavlovian Spontaneous Recovery [PSR]). Rats were then given a week in their home cage before being returned to the operant chambers with access to EtOH and water (relapse). Nicotine (0, 0.1, 0.3, or 1.0mg/kg) was injected subcutaneously immediately or 4hours prior to PSR or relapse testing. Results: Injections of nicotine immediately prior to testing reduced (5 to 10 responses PSR; 50 to 60 responses relapse), whereas injections of nicotine 4hours prior to testing increased (up to 150 responses for PSR; up to 400 responses for relapse with 1.0mg/kg dose) responses on the EtOH lever during PSR and relapse tests. Conclusions: The results of this study demonstrate that acute effects of nicotine on EtOH-seeking and relapse behaviors may be time dependent, with the immediate effects being a result of nicotine possibly acting as a substitute for EtOH, whereas with a delay of 4hours, priming effects of nicotine alterations in nicotinic receptors, and/or the effects of nicotine's metabolites (i.e., cotinine and nornicotine) may enhance the expression of EtOH-seeking and relapse behaviors.",
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AU - Dhaher, Ronnie

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N2 - Background: Alcohol is frequently co-abused with smoking. In humans, nicotine use can increase alcohol craving and consumption. The objectives of the current study were to assess the acute effects of nicotine on alcohol seeking and relapse at 2 different time points. Methods: Adult female alcohol-preferring (P) rats were trained in 2-lever operant chambers to self-administer 15% ethanol (EtOH) (v/v) and water on a concurrent fixed-ratio 5-fixed-ratio 1 (FR5-FR1) schedule of reinforcement in daily 1-hour sessions. Following 10weeks of daily 1-hour sessions, rats underwent 7 extinction sessions, followed by 2weeks in their home cages. Rats were then returned to the operant chambers without EtOH or water being present for 4 sessions (Pavlovian Spontaneous Recovery [PSR]). Rats were then given a week in their home cage before being returned to the operant chambers with access to EtOH and water (relapse). Nicotine (0, 0.1, 0.3, or 1.0mg/kg) was injected subcutaneously immediately or 4hours prior to PSR or relapse testing. Results: Injections of nicotine immediately prior to testing reduced (5 to 10 responses PSR; 50 to 60 responses relapse), whereas injections of nicotine 4hours prior to testing increased (up to 150 responses for PSR; up to 400 responses for relapse with 1.0mg/kg dose) responses on the EtOH lever during PSR and relapse tests. Conclusions: The results of this study demonstrate that acute effects of nicotine on EtOH-seeking and relapse behaviors may be time dependent, with the immediate effects being a result of nicotine possibly acting as a substitute for EtOH, whereas with a delay of 4hours, priming effects of nicotine alterations in nicotinic receptors, and/or the effects of nicotine's metabolites (i.e., cotinine and nornicotine) may enhance the expression of EtOH-seeking and relapse behaviors.

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