Effects of nicotine conditioning history on alcohol and methamphetamine self-administration in rats

Abstract

Background: Smoking constitutes a significant public health risk. Alcohol and methamphetamine use disorders are also highly co-morbid with smoking, further increasing negative health outcomes. An important question in determining the underlying neurobiology of nicotine poly-drug use is understanding whether having a positive history with nicotine effects alters later drug-taking behavior.

Methods: The current experiments sought to elucidate whether having an appetitive nicotine conditioning history would affect later alcohol or methamphetamine self-administration. Adult male and female Long-Evans rats were first trained on a discriminated goal-tracking task in which the interoceptive effects of nicotine predicted sucrose reinforcement. As a control, pseudo-conditioned groups were included that had equated nicotine and sucrose experience. Rats were then shifted to either alcohol self-administration or methamphetamine self-administration.

Results: Nicotine conditioning history had no effect on acquisition or maintenance of alcohol self-administration in males or females. In contrast, an appetitive nicotine conditioning history decreased methamphetamine self-administration in female rats, but not males.

Conclusions: In female, but not male, rats, an appetitive conditioning history with nicotine decreases methamphetamine, but not alcohol, self-administration. This dissociation suggests that the effects may be due to a specific increase in the reinforcing value of methamphetamine. This may have implications for better understanding the progression of drug use from nicotine to methamphetamine.

Figure 1.

Anticipatory head entry rate was greater on nicotine sessions compared to saline sessions. A) Mean(±SEM) head entries/sec prior to the first sucrose presentation (PreUS) for male nicotineCS and pseudoCS rats. NicotineCS trained males showed higher head entry rates on nicotine sessions than saline sessions, more consistently than pseudoCS males. B) Mean(±SEM) head entries/sec PreUS for the female nicotineCS and pseudoCS rats. NicotineCS trained females showed higher head entry rates on nicotine sessions compared to saline sessions. PseudoCS trained females did not differ between nicotine and saline sessions. *p< 0.05, nicotine session higher than saline session in nicotineCS group, +p < 0.05, nicotine session higher than saline session in pseudoCS group.

Figure 2.

Nicotine conditioning history did not affect acquisition of alcohol self-administration. A/B) Mean(±SEM) alcohol lever responses and alcohol intake (g/kg) respectively in male nicotineCS and pseudoCS groups. C/D) Mean(±SEM) alcohol lever responses and alcohol intake (g/kg) respectively in the female nicotineCS and pseudoCS groups. Alcohol intake did not differ between any group.

Figure 3.

Nicotine conditioning history did not affect alcohol self-administration. A/B) Mean(±SEM) alcohol lever responses and alcohol intake (g/kg) respectively in male nicotineCS and pseudoCS groups. C/D) Mean(±SEM) alcohol lever responses and alcohol intake (g/kg) respectively in the female nicotineCS and pseudoCS groups. Alcohol intake did not differ between any group.

Figure 4.

Anticipatory head entry rate was greater on nicotine sessions compared to saline sessions. A) Mean(±SEM) head entries/sec prior to the first sucrose presentation (PreUS) for male nicotineCS and pseudoCS rats. NicotineCS trained males showed higher head entry rates on nicotine sessions than saline sessions. PseudoCS trained males did not differ between nicotine and saline sessions. B) Mean(±SEM) head entries/sec PreUS for the female nicotineCS and pseudoCS rats. NicotineCS trained females showed higher head entry rates on nicotine sessions compared to saline sessions. PseudoCS trained females did not differ between nicotine and saline sessions. * p< 0.05, nicotine session higher than saline session in nicotineCS group.

Figure 5.

Prior appetitive conditioning history with nicotine as a CS selectively reduced methamphetamine intake in females. A) Mean(±SEM) methamphetamine infusion taken during self-administration in the male nicotineCS and pseudoCS groups. B) Mean(±SEM) methamphetamine infusion taken during self-administration in the female nicotineCS and pseudoCS groups. NicotineCS trained females self-administered less methamphetamine than the pseudoCS females. ^ - indicates significant main effect of Conditioning History, p = 0.001.