Varenicline decreases nicotine but not alcohol self-administration in genetically selected Marchigian Sardinian alcohol-preferring (msP) rats

Abstract

Background Alcohol and nicotine are largely co-abused. Here, we investigated whether concurrent exposure to both addictive drugs influences each other’s consumption and whether varenicline attenuates alcohol consumption in the presence of nicotine. Methods Marchigian Sardinian alcohol-preferring (msP) rats trained to simultaneously self-administer oral alcohol (10% v/v) and intravenous nicotine (30 μg/kg/inf.) were used. Additional groups of rats were trained to self-administer either alcohol or nicotine. Further, msP rats were also trained to self-administer nicotine followed by 22-h/day access to alcohol and water in a two bottle free choice paradigm or water alone. The effects of varenicline (0.0, 0.3, 1.0, 3.0 mg/kg, p.o.) on alcohol and nicotine consumption was tested. Results In a self-administration paradigm, msP rats showed a significantly high levels of alcohol and nicotine intake when the drugs were administered alone. However, when access to both drugs occurred concomitantly, the number of nicotine infusions self-administered was significantly decreased. Nicotine self-administration was markedly reduced by varenicline regardless of whether it was self-administered alone or concurrently with alcohol. In a two bottle choice test, varenicline significantly decreased nicotine self-administration but had no influence on alcohol consumption. Conclusion Varenicline is highly efficacious in decreaasing nicotine self-administration either alone or in combination with alcohol. However, varenicline failed to influence both operant responding for alcohol and home-cage alcohol drinking in msP animals. Taken together, our findings suggest that the effects of varenicline could be specific to nicotine under conditions where excessive alcohol drinking is facilitated by genetic factors as in msP rats.

Voluntary co-consumption of alcohol and nicotine: Effects of abstinence, intermittency, and withdrawal in mice

“…In studies of voluntary alcohol consumption and investigator-administered nicotine in rats and mice, nicotine injections can decrease (Blomqvist et al, 1996; Hendrickson et al, 2009; Hauser et al, 2012), or increase (Lê et al, 2000; Lê et al, 2003; Hauser et al, 2012; Sajja and Rahman, 2012) alcohol consumption depending on the genetic background, as well as the dose, timing and duration of the nicotine injection. In the few studies that have investigated coadministration of intravenous nicotine and oral alcohol in male rats, consumption of both drugs together result in decreased nicotine intake compared with rats self-administering nicotine alone, but self-administration of alcohol and nicotine together did not have an effect on the level of alcohol consumption (Lê et al, 2010; Scuppa et al, 2015). We found that in our continuous access tests of alcohol and nicotine co-consumption, male mice consumed less alcohol when nicotine was available, but the availability of alcohol did not affect nicotine consumption.…”

“…Very few groups have performed studies of voluntary oral alcohol and intravenous nicotine self-administration in male rats (Lê et al, 2010; Lê et al, 2014; Scuppa et al, 2015). Due to the technical challenges of intravenous self-administration in mice, nicotine consumption is most often studied using voluntary oral consumption procedures (Klein et al, 2004; Lee and Messing, 2011; Locklear et al, 2012).…”

Mechanisms and genetic factors underlying co-use of nicotine and alcohol or other drugs of abuse

“…Despite evidence that varenicline decreases alcohol intake (100,108,129), the effects on co-self-administration of nicotine and alcohol are not as clear (130,131). However, withdrawal from chronic concurrent exposure, which is more prolonged than withdrawal from either drug alone, can be attenuated by continued treatment with just one of the drugs (132).…”

The effects of varenicline on methamphetamine self-administration and drug-primed reinstatement in female rats

“…Similarly, some studies have reported reduced intake of ethanol(see Table 2; Feduccia et al , 2014; Ginsburg and Lamb, 2013; Hendrickson et al , 2010; Kamens et al , 2010; Kaminski and Weerts, 2014; Randall et al , 2015; Sotomayor-Zárate et al , 2013; Steensland et al , 2007; Wouda et al , 2011). Interestingly, other published reports have either shown no effect on ethanol intake (Scuppa et al, 2015),or an increase in ethanol intake at certain doses (Ginsburg and Lamb, 2013). Pre-clinical research isalso mixed regarding the effects of varenicline on cocaine self-administration (see Table 3), with investigators reporting a decrease in intake (Guillem and Peoples, 2010), no effect on intake(Mello et al , 2014), oran increase in cocaine intake (Gould et al , 2011).…”

“…Varenicline is a partial α4β2 and full α7 nAChR agonist (Coe et al , 2005a; Coe et al , 2005b; Gonzales et al , 2006; Mihalak et al , 2006; Smith et al , 2007) currently approved by the United States Food and Drug Administration for treatment of nicotine dependence under the trade name Chantix ® . As detailed in Table 1, pretreatment with varenicline reduces nicotine self-administrationin pre-clinical models, (see Table 1; Chang et al , 2015; Costello et al , 2014; Funk et al , 2015; George et al , 2011; Goeders et al , 2012; Hall et al , 2015; Le Foll et al , 2012; Mello et al , 2014; O'Connor et al , 2010; Panlilio et al , 2015; Rollema et al , 2007; Scuppa et al , 2015; Wouda et al , 2011). Similarly, some studies have reported reduced intake of ethanol(see Table 2; Feduccia et al , 2014; Ginsburg and Lamb, 2013; Hendrickson et al , 2010; Kamens et al , 2010; Kaminski and Weerts, 2014; Randall et al , 2015; Sotomayor-Zárate et al , 2013; Steensland et al , 2007; Wouda et al , 2011).…”