Rewarding Effects of Nicotine Self-administration Increase Over Time in Male and Female Rats

Abstract

Smoking and the use of other nicotine-containing products is rewarding in humans. The self-administration of nicotine is also rewarding in male rats. However, it is unknown if there are sex differences in the reward-enhancing effects of nicotine self-administration and if the rewarding effects of nicotine change over time. Rats were prepared with catheters and intracranial self-stimulation (ICSS) electrodes to investigate the effects of nicotine and saline self-administration on reward function. A decrease in thresholds in the ICSS procedure reflects an enhancement of reward function. The ICSS parameters were determined before and after the self-administration sessions from day 1 to 10, and after the self-administration sessions from day 11 to 15. During the first 10 days, there was no sex difference in nicotine intake, but during the last 5 days, the females took more nicotine than the males. During the first 10 days, nicotine self-administration did not lower the brain reward thresholds but decreased the response latencies. During the last 5 days, nicotine lowered the reward thresholds and decreased the response latencies. An analysis with the 5-day averages (Day 1-5, 6-10, and 11-15) showed that the reward enhancing and stimulatory effects of nicotine increased over time. There were no sex differences in the reward-enhancing and stimulatory effects of nicotine. The nicotinic receptor antagonist mecamylamine diminished the reward-enhancing and stimulatory effects of nicotine. Overall, these findings indicate that the rewarding effects of nicotine self-administration increase over time, and there are no sex differences in the reward-enhancing effects of nicotine self-administration in rats.

The D1/D2-like receptor antagonist flupentixol and the D2-like receptor antagonist L-741626 decrease operant responding for nicotine and food and locomotor activity in male and female rats

“…In a recent study with a similar design (food training followed by IV nicotine intake) and nicotine dose (0.06 mg/kg/inf), we did not observe a sex difference in nicotine intake (Chellian et al, 2022). In other studies, in which the rats were trained to respond for food pellets before the self-administration of a lower dose of nicotine, 0.03 mg/kg/inf, we also did not observe a sex difference in nicotine intake (Chellian et al, 2020a; Chellian et al, 2021b). In a study in which we investigated the spontaneous acquisition of nicotine self-administration (no prior food training), the females self-administered more nicotine than the males (Chellian et al, 2021c).…”

“…The catheters were implanted as described before (Chellian et al, 2021b; Chellian et al, 2021c). The rats were anesthetized with an isoflurane-oxygen vapor mixture (1–3%) and prepared with a catheter in the right jugular vein.…”

Adult consequences of repeated nicotine vapor inhalation in adolescent rats

“…There is also varied evidence of female Sprague-Dawley rats self-administering / acquiring more / faster (Sanchez et al, 2014), less/slower (Levin et al, 2011) or the same (Chaudhri et al, 2005; Donny et al, 2000; Pittenger et al, 2016) as male rats of the same strain. Similarly, female Wistar rats have been reported as self-administering / acquiring more / faster (Chellian et al, 2021; Uribe et al, 2020), less/slower (Swalve et al, 2016) or the same as male rats of the same strain and a similar diversity of sex-associated outcome has been reported for Long Evans rats (Leyrer-Jackson et al, 2021; Li et al, 2014). Another study found that female rats intravenously self-administer higher amounts of nicotine only under FR5, but not FR1, and as in the present study, responses only partially compensated (i.e.12-19 responses under FR1, 30-70 under FR5) for the increased response requirement (Chaudhri et al, 2005).…”

Dopamine D1‐like receptor activation decreases nicotine intake in rats with short or long access to nicotine

“…The catheters were implanted as described before 26,36,37 . The rats were anaesthetised with an isoflurane‐oxygen vapour mixture (1–3%) and prepared with a catheter in the right jugular vein.…”

“…Our prior work showed that rats with long access to nicotine increased their nicotine intake over time and gradually consumed a higher proportion of nicotine during the light phase, which might be a sign of dependence 24,25 . Nicotine self‐administration facilitates intracranial self‐stimulation (ICSS) in rats, which indicates that nicotine enhances brain reward function 24,26 . Drugs that facilitate ICSS may have abuse potential in humans 27 .…”