Time-course of extracellular nicotine and cotinine levels in rat brain following administration of nicotine

Effects of route and ethanol coadministration

Simon N. Katner, Jamie E. Toalston, Michael P. Smoker, Zachary Rodd, William J. McBride, Eric Engleman

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Rationale: Nicotine and ethanol are commonly coabused drugs, and nicotine-laced ethanol products are growing in popularity. However, little is known about time-course changes in extracellular nicotine and cotinine levels in rat models of ethanol and nicotine coabuse. Objectives: The objective of the present study was to determine the time-course changes in brain levels of nicotine and cotinine following subcutaneous (SC) and intragastric (IG) nicotine administration in alcohol-preferring (P) and Wistar rats. Methods: In vivo microdialysis was used to collect dialysate samples from the nucleus accumbens shell (NACsh) for nicotine and cotinine determinations, following SC administration of (-)-nicotine (0.18, 0.35, and 0.70 mg/kg) in female P and Wistar rats or IG administration of (-)-nicotine (0.35 and 0.70 mg/kg) in 15 % (v/v) ethanol or water in female P rats. Results: SC nicotine produced nicotine and cotinine dialysate levels as high as 51 and 14 ng/ml, respectively. IG administration of 15 % EtOH∈+∈0.70 mg/kg nicotine in P rats resulted in maximal nicotine and cotinine dialysate levels of 19 and 14 ng/ml, respectively, whereas administration of 0.70 mg/kg nicotine in water resulted in maximal nicotine and cotinine levels of 21 and 25 ng/ml, respectively. Nicotine and cotinine levels were detectable within the first 15 and 45 min, respectively, after IG administration. Conclusions: Overall, the results of this study suggest that nicotine is rapidly adsorbed and produces relevant extracellular brain concentrations of nicotine and its pharmacologically active metabolite, cotinine. The persisting high brain concentrations of cotinine may contribute to nicotine addiction.

Original languageEnglish
Pages (from-to)551-560
Number of pages10
JournalPsychopharmacology
Volume232
Issue number3
DOIs
StatePublished - 2015

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Cotinine
Nicotine
Ethanol
Brain
Dialysis Solutions
Wistar Rats

Keywords

  • Alcohol
  • Brain
  • Metabolism
  • Microdialysis
  • Nicotine
  • Nucleus accumbens
  • Rat

ASJC Scopus subject areas

  • Pharmacology

Cite this

Time-course of extracellular nicotine and cotinine levels in rat brain following administration of nicotine : Effects of route and ethanol coadministration. / Katner, Simon N.; Toalston, Jamie E.; Smoker, Michael P.; Rodd, Zachary; McBride, William J.; Engleman, Eric.

In: Psychopharmacology, Vol. 232, No. 3, 2015, p. 551-560.

Research output: Contribution to journalArticle

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title = "Time-course of extracellular nicotine and cotinine levels in rat brain following administration of nicotine: Effects of route and ethanol coadministration",
abstract = "Rationale: Nicotine and ethanol are commonly coabused drugs, and nicotine-laced ethanol products are growing in popularity. However, little is known about time-course changes in extracellular nicotine and cotinine levels in rat models of ethanol and nicotine coabuse. Objectives: The objective of the present study was to determine the time-course changes in brain levels of nicotine and cotinine following subcutaneous (SC) and intragastric (IG) nicotine administration in alcohol-preferring (P) and Wistar rats. Methods: In vivo microdialysis was used to collect dialysate samples from the nucleus accumbens shell (NACsh) for nicotine and cotinine determinations, following SC administration of (-)-nicotine (0.18, 0.35, and 0.70 mg/kg) in female P and Wistar rats or IG administration of (-)-nicotine (0.35 and 0.70 mg/kg) in 15 {\%} (v/v) ethanol or water in female P rats. Results: SC nicotine produced nicotine and cotinine dialysate levels as high as 51 and 14 ng/ml, respectively. IG administration of 15 {\%} EtOH∈+∈0.70 mg/kg nicotine in P rats resulted in maximal nicotine and cotinine dialysate levels of 19 and 14 ng/ml, respectively, whereas administration of 0.70 mg/kg nicotine in water resulted in maximal nicotine and cotinine levels of 21 and 25 ng/ml, respectively. Nicotine and cotinine levels were detectable within the first 15 and 45 min, respectively, after IG administration. Conclusions: Overall, the results of this study suggest that nicotine is rapidly adsorbed and produces relevant extracellular brain concentrations of nicotine and its pharmacologically active metabolite, cotinine. The persisting high brain concentrations of cotinine may contribute to nicotine addiction.",
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T1 - Time-course of extracellular nicotine and cotinine levels in rat brain following administration of nicotine

T2 - Effects of route and ethanol coadministration

AU - Katner, Simon N.

AU - Toalston, Jamie E.

AU - Smoker, Michael P.

AU - Rodd, Zachary

AU - McBride, William J.

AU - Engleman, Eric

PY - 2015

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N2 - Rationale: Nicotine and ethanol are commonly coabused drugs, and nicotine-laced ethanol products are growing in popularity. However, little is known about time-course changes in extracellular nicotine and cotinine levels in rat models of ethanol and nicotine coabuse. Objectives: The objective of the present study was to determine the time-course changes in brain levels of nicotine and cotinine following subcutaneous (SC) and intragastric (IG) nicotine administration in alcohol-preferring (P) and Wistar rats. Methods: In vivo microdialysis was used to collect dialysate samples from the nucleus accumbens shell (NACsh) for nicotine and cotinine determinations, following SC administration of (-)-nicotine (0.18, 0.35, and 0.70 mg/kg) in female P and Wistar rats or IG administration of (-)-nicotine (0.35 and 0.70 mg/kg) in 15 % (v/v) ethanol or water in female P rats. Results: SC nicotine produced nicotine and cotinine dialysate levels as high as 51 and 14 ng/ml, respectively. IG administration of 15 % EtOH∈+∈0.70 mg/kg nicotine in P rats resulted in maximal nicotine and cotinine dialysate levels of 19 and 14 ng/ml, respectively, whereas administration of 0.70 mg/kg nicotine in water resulted in maximal nicotine and cotinine levels of 21 and 25 ng/ml, respectively. Nicotine and cotinine levels were detectable within the first 15 and 45 min, respectively, after IG administration. Conclusions: Overall, the results of this study suggest that nicotine is rapidly adsorbed and produces relevant extracellular brain concentrations of nicotine and its pharmacologically active metabolite, cotinine. The persisting high brain concentrations of cotinine may contribute to nicotine addiction.

AB - Rationale: Nicotine and ethanol are commonly coabused drugs, and nicotine-laced ethanol products are growing in popularity. However, little is known about time-course changes in extracellular nicotine and cotinine levels in rat models of ethanol and nicotine coabuse. Objectives: The objective of the present study was to determine the time-course changes in brain levels of nicotine and cotinine following subcutaneous (SC) and intragastric (IG) nicotine administration in alcohol-preferring (P) and Wistar rats. Methods: In vivo microdialysis was used to collect dialysate samples from the nucleus accumbens shell (NACsh) for nicotine and cotinine determinations, following SC administration of (-)-nicotine (0.18, 0.35, and 0.70 mg/kg) in female P and Wistar rats or IG administration of (-)-nicotine (0.35 and 0.70 mg/kg) in 15 % (v/v) ethanol or water in female P rats. Results: SC nicotine produced nicotine and cotinine dialysate levels as high as 51 and 14 ng/ml, respectively. IG administration of 15 % EtOH∈+∈0.70 mg/kg nicotine in P rats resulted in maximal nicotine and cotinine dialysate levels of 19 and 14 ng/ml, respectively, whereas administration of 0.70 mg/kg nicotine in water resulted in maximal nicotine and cotinine levels of 21 and 25 ng/ml, respectively. Nicotine and cotinine levels were detectable within the first 15 and 45 min, respectively, after IG administration. Conclusions: Overall, the results of this study suggest that nicotine is rapidly adsorbed and produces relevant extracellular brain concentrations of nicotine and its pharmacologically active metabolite, cotinine. The persisting high brain concentrations of cotinine may contribute to nicotine addiction.

KW - Alcohol

KW - Brain

KW - Metabolism

KW - Microdialysis

KW - Nicotine

KW - Nucleus accumbens

KW - Rat

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