Influence of Menstrual Cycle Phase on Neural and Craving Responses to Appetitive Smoking Cues in Naturally Cycling Females

Introduction: Functional magnetic resonance imaging (fMRI) has been used extensively in an attempt to understand brain vulnerabilities that mediate maladaptive responses to drug cues. Using perfusion fMRI, we have consistently shown reward-related activation (medial orbitofrontal cortex/ventral striatum) to smoking cues (SCs). Because preclinical and clinical studies generally show that progesterone may reduce reward and craving, we hypothesized that females in the follicular phase of the cycle (FPs; when progesterone levels are low) would have greater reward-related neural responses to SCs compared with females in the luteal phase (LPs). Methods: Sated cigarette-dependent premenopausal naturally cycling females underwent pseudo-continuous arterial spin-labeled perfusion fMRI during exposure to 10-min audio visual clips of appetitive SCs and non-SCs. Brain responses to SCs relative to non-SCs were examined among females grouped according to menstrual cycle (MC) phase at the time of scanning (22 FPs, 15 LPs). Craving scores were acquired pre-and post-SC exposure. Results: FPs showed increased neural responses to SCs compared with non-SCs in the medial orbitofrontal cortex (p <= .05(corrected)), whereas LPs did not. FPs reported SC-elicited craving (p <= .005), whereas LPs did not. Within FPs, SC-induced craving correlated with increased neural responses in the anterior insula (r = 0.73, p < .0001). Conclusions: FPs may be more vulnerable to relapse during appetitive SC exposure than LPs. Because the influence of MC phase on drug cue neural activity has not been examined, these results contribute to our knowledge of the neurobiological underpinnings of responses to drug cues, and they highlight the importance of monitoring menstrual cycle phase in all areas of addiction research.