Sex and menstrual cycle effects on chronic oral cocaine self-administration in rhesus monkeys: Effects of a nondrug alternative reward

Abstract

Background In previous studies female monkeys self-administered more oral phencyclidine (PCP) than males, and PCP intake differed by phase of menstrual cycle. Objectives The purpose of this study was to examine sex and hormonal influences on oral cocaine self-administration in male and female rhesus monkeys in the follicular vs. luteal phases of the menstrual cycle, with concurrent access to an alternative nondrug reward, saccharin (SACC) vs. water. Materials and methods Concurrent access to cocaine (0.2, 0.4 and 0.8 mg/ml) and SACC or water was available from two drinking spouts under concurrent fixed-ratio (FR) 2, 4, and 8 schedules during daily 3-h sessions. Results Cocaine deliveries were similar in males and females in the females’ luteal phase, but cocaine deliveries were higher in females during the follicular phase than the luteal phase and compared to males. When SACC was available cocaine deliveries were reduced in females in the follicular phase of the cycle, and cocaine intake (mg/kg) was reduced in males and in females’ follicular and luteal phases. Conclusions Access to concurrent SACC (vs. water) reduced cocaine intake (mg/kg) in males and in females during both menstrual phases, and the magnitude of the reduction in cocaine intake was greatest during the females’ follicular phase. Thus, a nondrug alternative reward, SACC, is a viable alternative treatment for reducing cocaine’s rewarding effects on male and female monkeys, and reductions in cocaine-seeking were optimal in the females’ luteal phase.

Exercise or saccharin during abstinence block estrus-induced increases in nicotine-seeking

“…This addresses a limitation of our previous work using locked versus unlocked wheel access (Sanchez et al 2014;Peterson et al 2014), as well as previous work from others examining the effects of environmental enrichment (Solinas et al 2010), where it has not been possible to determine the contribution of exercise versus enrichment effects. Saccharin and other sweet rewards have been shown to reduce drugtaking when concurrently available with the drug (Carroll et al 2016), with results demonstrating that rats show an almost exclusive preference for saccharin versus drug under choice procedures (Cantin et al 2010;Huynh et al 2017). In fact, numerous recent studies have used saccharin solution and other highly palatable solutions as an alternative choice to the drug, including nicotine, as a means to maintain voluntary abstinence (Cantin et al 2010;Huynh et al 2017).…”

Sex differences, gender and addiction

“…As a result, findings remain incomplete and sometimes contradictory, particularly when the LGBT community is considered (Hughes et al 2016). Nevertheless, humans, monkeys and rodents exhibit similar sex differences in addiction-like behavior (Carroll et al 2005; Carroll et al 2016; Becker et al 2012) and biological sex differences can affect addiction-like behavior differently for males and females (Becker et al 2012; Perry et al 2013a). Effects of the environment and positive or negative experience can also affect the brain and influence vulnerability to addiction differently in males and females (Bowman et al 2004; Thomas et al 2009; Carroll et al 2009).…”

Insights from Preclinical Choice Models on Treating Drug Addiction

“…The role of sex as a determinant of preclinical drug versus nondrug choice has been recently investigated in both rats [65,102–104] and monkeys [105], and these results suggest two main findings. First, there was no effect of estrous cycle on intravenous cocaine versus food choice in rats or an effect of menstrual cycle on oral cocaine versus saccharin choice in monkeys.…”