Generalization of a positive-feature interoceptive morphine occasion setter across the rat estrous cycle.

INTRODUCTION: Interoceptive stimuli elicited by drug administration acquire conditioned modulatory properties of the induction of conditioned appetitive behaviours by exteroceptive cues. This effect may be modeled using a drug discrimination task in which the drug stimulus is trained as a positive-feature (FP) occasion setter (OS) that disambiguates the relation between an exteroceptive light conditioned stimulus (CS) and a sucrose unconditioned stimulus (US). We previously reported that females are less sensitive to generalization of a FP morphine OS than males, so we investigated the role of endogenous ovarian hormones in this difference. METHODS: Male and female rats received intermixed injections of 3.2 mg/kg morphine or saline before each daily training session. Training consisted of 8 presentations of the CS, each followed by access to sucrose on morphine, but not saline sessions. Following acquisiton, rats were tested for generalization of the morphine stimulus to 0, 1.0, 3.2, and 5.4 mg/kg morphine. Female rats were monitored for estrous cyclicity using vaginal cytology throughout the study. RESULTS: Both sexes acquired stable drug discrimination. A gradient of generalization was measured across morphine doses and this behaviour did not differ by sex, nor did it differ across the estrous cycle in females. CONCLUSIONS: Morphine generalization is independent of fluctuations in levels of sex and endogenous gonadal hormones in females under these experimental conditions.

Sex Differences in the Behavioural Outcomes of Prenatal Nicotine and Tobacco Exposure.

Smoking remains the leading cause of preventable death worldwide. A combination of biological and environmental risk factors make women especially vulnerable to nicotine addiction, making it harder for them to quit smoking. Smoking during pregnancy, therefore, is still a major health concern, with epidemiological data suggesting a role for gestational nicotine exposure in the development of several behavioural disorders. Given there are significant sex-specific behavioural outcomes related to smoking in adolescence and adulthood, it is probable that the behavioural outcomes following gestational nicotine or tobacco exposure are similarly sex-dependent. This is an especially relevant topic as the current landscape of nicotine use shifts toward vaping, a mode of high doses of nicotine delivery that is largely believed to be a safer alternative to cigarettes among the public as well as among pregnant women. Here we review existing clinical and preclinical findings regarding the sex-dependent behavioural outcomes of prenatal nicotine exposure. We also highlight the challenges within this literature, particularly those areas in which further research is necessary to improve consistency within, and between, clinical and preclinical findings.