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.

Effects of nicotine and THC vapor inhalation administered by an electronic nicotine delivery system (ENDS) in male rats

“…The plasma analysis found that nicotine and cotinine levels 15 minutes after subcutaneous injection of 0.8 mg/kg were similar to those observed after 15 minutes of inhalation of vapor from 30 mg/mL in this study. The nicotine and cotinine levels were similar to intracerebral dialysate levels of nicotine and cotinine after subcutaneous injection of 0.7 mg/kg in Wistar rats (Katner et al, 2015) and plasma levels after a 0.03 mg/kg intravenous injection in Wistar rats (de Villiers et al, 2004). Concentrations of nicotine and cotinine in the plasma observed after 30 minutes of inhalation were significantly higher than those observed after 15 minutes of inhalation, confirming the control of dose via inhalation duration.…”

Effects of Nicotine and THC Vapor Inhalation Administered by An Electronic Nicotine Delivery System (ENDS) in Male Rats

“…The plasma analysis found that nicotine and cotinine levels 15 minutes after subcutaneous injection of 0.8 mg/kg were similar to those observed after 15 minutes of inhalation of vapor from 30 mg/mL in this study. The nicotine and cotinine levels were similar to intracerebral dialysate levels of nicotine and cotinine after subcutaneous injection of 0.7 mg/kg in Wistar rats (Katner et al 2015) and plasma levels after a 0.03 mg/kg intravenous injection in Wistar rats (de Villiers et al 2004).…”

Nicotine and ethanol co-use in Long-Evans rats: Stimulatory effects of perinatal exposure to a fat-rich diet

“…Although nicotine levels were not measured in this study, extrapolation from data obtained in other nicotine self-administration studies (LeSage, Keyler, Collins, & Pentel, 2003; Shoaib & Stolerman, 1999) suggests that blood nicotine levels in the chow group are likely to be around 65 ng/mL, which is comparable to nicotine levels in smokers (Benowitz & Jacob, 1984). A recent study, showing that ethanol can affect nicotine accumulation in the brain, is consistent with the idea that ethanol is involved in nicotine addiction (Katner et al, 2015). …”