Increased Vulnerability to Nicotine Self-Administration and Relapse in Alcohol-Naive Offspring of Rats Selectively Bred for High Alcohol Intake

Abstract

The prevalence of smoking in human alcoholics is substantially higher than in the general population, and results from twin studies suggest that a shared genetic vulnerability underlies alcohol and nicotine addiction. Here, we directly tested this hypothesis by examining nicotine-taking behavior in alcohol-naive offspring of alcohol-preferring (P) rats and alcohol-nonpreferring (NP) rats that had been selectively bred for high and low alcohol intake. The self-administration of intravenous nicotine (0.015-0.060 mg/kg per infusion) in P rats was more than twice than that of NP rats. Nicotine seeking induced by reexposure to nicotine cues in extinction tests was also substantially greater in P rats than in NP rats. In a subsequent relapse test, priming nicotine injections reinstated drug seeking in P rats but not NP rats. P rats also self-administered higher amounts of oral sucrose (1-20%) than NP rats, a finding consistent with previous reports. In contrast, self-administration of intravenous cocaine (0.1875-1.125 mg/kg per infusion) was remarkably similar in the P and NP rats; however, P-NP differences in cocaine seeking emerged in subsequent extinction and cocaine priming-induced reinstatement tests. In both cases, lever responding was higher in P rats than in NP rats. Thus, alcohol-naive offspring of rats genetically selected for high alcohol intake are highly susceptible to nicotine self-administration and relapse, and this susceptibility is not likely caused by general reward deficits in NP rats. The present findings provide experimental evidence for the hypothesis that a shared genetic determinant accounts for the co-abuse of nicotine and alcohol.

Nicotine Self-Administration, Extinction Responding and Reinstatement in Adolescent and Adult Male Rats: Evidence Against a Biological Vulnerability to Nicotine Addiction during Adolescence

“…Adult rats showed a dose-dependent decrease in nicotine self-administration, a finding consistent with previous reports (Corrigall and Coen, 1989;Shoaib et al, 1997;Watkins et al, 1999;Le et al, 2006). In contrast, increasing the nicotine dose had minimal effect on responding in adolescent rats.…”

“…For both age groups, nicotine priming injections reliably reinstated nicotine seeking, an observation consistent with previous reports (Shaham et al, 1997;Le et al, 2006). The mechanisms underlying nicotineinduced reinstatement are unknown.…”

“…Buprenorphine (0.01 mg/kg, s.c.) was administered as an analgesic and penlong (15 000 (juvenile) or 30 000 U (adult), i.m., Rogar/STP, London, ON, Canada) was used as antibiotic treatment. Juvenile (P26-28) and adult rats (P80-87) were prepared with catheters implanted into the right jugular vein as described previously (Corrigall and Coen, 1989;Le et al, 2006). The catheter exited between the scapulae and was attached to the modified 22-gauge cannula that connected to the fluid swivel system.…”

“…The unit doses for nicotine selfadministration were 0.015, 0.03 and 0.06 mg/kg/infusion, expressed as base (Corrigall and Coen, 1989;Shoaib and Stolerman, 1999;Le et al, 2006). During the tests for reinstatement, nicotine (0.075, 0.15, 0.3 mg/kg) was administered subcutaneously in a volume of 1 ml/kg (Shaham et al, 1997;Le et al, 2006). Catheter patency was tested after each experimental phase using the rapid acting anesthetic, sodium methohexital (0.05 mg/kg, i.v., 10 mg/ml).…”

Effects of Cigarette Smoking and Family History of Alcoholism on Sweet Taste Perception and Food Cravings in Women

“…The comorbidity of alcohol and nicotine dependence and the associations of these 2 drugs of abuse with sweet taste preferences may be attributed to common neurobiological bases of reward (Levine et al, 2003), pharmacological interactions resulting in one drug facilitating the other (Acheson et al, 2006), and/or shared genetic factors (see Li et al, 2007). Rats genetically selected for high alcohol consumption are more sensitive to the rewarding properties of nicotine (Le et al, 2006) than rats genetically selected for low alcohol consumption. Likewise, consumption of sweet-tasting solutions predicts alcohol intake among rodent strains and within their segregating crosses (Bachmanov et al, 1996) and alcoholpreferring animals find sucrose more rewarding than animals that show low preference to alcohol (Le et al, 2006).…”