Menstrual cycle phase modulates responses to smoking cues in the putamen: Preliminary evidence for a novel target

Abstract

Background: The preclinical literature identifies the ventral striatum (VS) as a key player in drug-conditioned responses, guiding hypotheses examining neural substrates involved in human drug cue reactivity, including the study of sex differences. Men show a replicable response that includes the VS, while women's responses have been weaker and variable. New evidence suggests that the hormonal milieu modulates women's responses to drug cues in the dorsal striatum (DS), specifically, in the putamen. Here we tested the hypothesis that the hormonal milieu affects neural responses to smoking cues (SCs) in the putamen in women cigarette smokers. Methods: We reexamined our three previous neuroimaging studies of the influence of sex and menstrual cycle (MC) phase effects on SC neuroactivity, incorporating the DS as a region of interest. Results: As previously shown, men exhibited increased ventral medial prefrontal cortex (vmPFC) and VS/V pallidum responses, and women showed increased vmPFC responses that were greater in women during the follicular phase (high estradiol), compared to the luteal phase (high progesterone). Reducing the statistical threshold within luteal phase women revealed select deactivation of the putamen. Conclusions: These preliminary findings shed light upon factors that may modulate drug cue reactivity in women, specifically the influence of hormones on DS responses. Emerging literature suggests that manipulating the hormonal milieu may open a fundamental window into sex-specific treatment targets. More rigorous study of the brain substrates involved in drug cue reactivity and

Neural Basis of Increased Cognitive Control of Impulsivity During the Mid-Luteal Phase Relative to the Late Follicular Phase of the Menstrual Cycle

“…Moreover, women showed greater activation in the right DS (putamen and caudate) when choosing sooner rewards in the late FP than when do so in the mid-LP (i.e., SFP > SLP), indicating that the right DS is more responsive to immediate rewards during the late FP than during the mid-LP. These results are consistent with the prior findings showing that a heightened drug cue-responsivity in women is associated with enhanced activity in the DS, especially in the putamen ( Cummings et al, 2014 ; Franklin et al, 2019 ). Indeed, behavioral impulsivity has been linked to dopamine levels in the putamen.…”

“…Region of interest analyses were conducted to further refine our hypothesis. ROIs were selected based on our hypotheses and previous studies ( Cummings et al, 2014 ; Franklin et al, 2019 ). Based on prior relevant work ( Pine et al, 2010 ), the following Montreal Neurological Institute (MNI) coordinates for bilateral ROIs were defined: putamen, MNI coordinates 30 −3 −12 and −24 12 −9; caudate, MNI coordinates 21 24 −3 and −9 12 9; and dlPFC, MNI coordinates 42 18 27 and −45 33 18.…”

“…Cummings et al’s results (2014) suggested that estradiol enhances dopamine release in the DS, but not ventral striatum (VS), in female rats. A recent study showed that women’s responses to drug cues in the DS, specifically in the putamen, were modulated by menstrual phase ( Franklin et al, 2019 ).…”

A Methodological Checklist for fMRI Drug Cue Reactivity Studies: Development and Expert Consensus

“…In terms of sex/gender, multiple studies have demonstrated sex- /gender-related differences in FDCR, particularly in participants who smoke cigarettes (Francis J. McClernon, Kozink, & Rose, 2008; Wetherill et al, 2013), individuals with cocaine dependence (Joseph et al, 2019; Potenza et al, 2012), and those with gambling (Kober et al, 2016) and gaming (Dong, Wang, Du, & Potenza, 2018; Dong, Wang, Wang, Du, & Potenza, 2019; Dong, Zheng, et al, 2018) disorders, which may depend, in part, on menstrual cycle phase in women (T. R. Franklin, Jagannathan, Ketcherside, Spilka, & Wetherill, 2019).…”

“…Because older adults have been routinely excluded from MRI studies that do not focus on aging, and taking into account shared neurodegenerative impacts of addiction and biological aging (Cheng et al, 2013), there is relatively little known about FDCR in older adults (e.g., > 65-years). In terms of sex/gender, multiple studies have demonstrated sex-/gender-related differences in FDCR, particularly in participants who smoke cigarettes (Francis J. McClernon, Kozink, & Rose, 2008;Wetherill et al, 2013), individuals with cocaine dependence (Joseph et al, 2019;Potenza et al, 2012), and those with gambling (Kober et al, 2016) and gaming Dong, Wang, Wang, Du, & Potenza, 2019;Dong, Zheng, et al, 2018) disorders, which may depend, in part, on menstrual cycle phase in women (T. R. Franklin, Jagannathan, Ketcherside, Spilka, & Wetherill, 2019).…”