Sex differences in the contribution of nicotine and nonpharmacological stimuli to nicotine self-administration in rats
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Sex differences have been reported for the impact of nicotine and nonpharmacological cues on smoking. While nonpharmacological environmental stimuli have also been shown to influence nicotine self-administration in rats, there have been no attempts to examine the impact of sex differences in the contributions of nicotine and nondrug stimuli to this behavior.
This experiment investigated sex differences in operant responding for nicotine in rats when drug infusions were delivered either in the absence of, or in combination with, a nonpharmacological stimulus.
Initially, male and female rats acquired self-administration for nicotine alone across a range of doses (0.03, 0.06, and 0.15 mg kg−1 inf−1, freebase). After stable acquisition, nicotine infusions were combined with a weakly reinforcing, compound visual stimulus.
While there was no overall effect of dose on active lever responding for nicotine in the absence of the visual stimulus, female rats responded more on the reinforced lever than males at 0.06 and 0.15 mg kg−1 inf−1 on an FR5 schedule. However, they also showed increased responding on the nonreinforced lever compared to males at the same doses. Combining nicotine infusions with the visual stimulus doubled responding compared to nicotine alone at 0.03 and 0.06, but not at 0.15 mg kg−1 inf−1: this effect was significantly greater for female rats.
These data highlight the prominent contribution of nonpharmacological stimuli to nicotine-reinforced behavior across a range of doses in both male and female rats. They also reveal sex differences in operant responding for nicotine under conditions where a nonpharmacological stimulus is either absent, or combined with drug delivery.
KeywordsNicotine Sex differences Self-administration Environmental Nonpharmacological stimulus Dose response
This work was supported by National Institute on Drug Abuse research grants, DA-10464 and DA-12655, and by a Howard Hughes Predoctoral Research Fellowship awarded to N. Chaudhri. “Principles of laboratory animal care” (NIH No. 85-23, revised 1985) were followed throughout all experiments. The University of Pittsburgh Institutional Animal Care and Use Committee, Assurance Number A3187-01 approved this research. N. Chaudhri can be contacted at email@example.com.
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