Effect of menstrual cycle on rewarding properties of alcohol cues in women.

OBJECTIVE: Compared with men, women are disproportionately affected by alcohol, including greater risks of behavioral impairment and relapse from abstinence-based treatments. One potential mechanism underlying this disparity is ovarian hormone fluctuations across menstrual cycle phases, particularly estradiol (E2). Preclinical and clinical studies have shown that E2 levels positively correlate with alcohol consumption, suggesting E2 modulates drinking. Rewarding properties of alcohol are thought to mediate this relationship. The present study tested the degree to which women report increased rewarding effects from alcohol and heightened attention to alcohol-related cues when E2 was elevated during the late follicular phase of the menstrual cycle. METHOD: Fifty women aged 21-29 participated in a within-subjects placebo-controlled study examining how menstrual cycle phase alters the rewarding properties of alcohol and alcohol-associated cues when sober and intoxicated, as measured by their attentional bias toward alcohol-associated cues and subjective reports. Measures were obtained following 0.60 g/kg alcohol and placebo during the early follicular phase when E2 was low and the late follicular phase (i.e., ovulation) when E2 was elevated. RESULTS: Attentional bias to alcohol-associated cues was greater during the late follicular phase in both sober and intoxicated states. Women reported rewarding effects from alcohol, but no effects of phase were observed. CONCLUSIONS: The findings suggest that the rewarding properties of alcohol-associated cues might be enhanced during the late follicular phase of the menstrual cycle when E2 is elevated, possibly increasing the risk for excessive drinking in women during this phase. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Heightened sensitivity to the disinhibiting effect of alcohol in women during the late follicular phase of the menstrual cycle.

Compared with men, women are disproportionately affected by alcohol, including greater risks of physiological damage, behavioral impairment, and relapse. One likely mechanism underlying the sexual disparity in this vulnerability is the fluctuation of ovarian hormones, particularly estradiol (E2), across phases of the menstrual cycle. Several preclinical and clinical studies have shown that higher E2 levels positively correlate with drinking, suggesting E2 may play a significant role in modulating drinking. Inhibitory control also modulates drinking; when it is reduced or compromised by alcohol, the drinker's ability to stop the self-administration of alcohol could be impaired, leading to a binge episode. The present study aimed to examine the degree to which menstrual cycle phase can influence the disinhibiting effect of alcohol. Twenty-four healthy young adult women participated in a within-subjects placebo-controlled study of the acute disinhibiting effect of 0.60 g/kg alcohol over the course of two test sessions. A cued go/no-go task measured the disinhibiting effects of alcohol and placebo beverages during the early follicular phase of the cycle when E2 levels were low and the late follicular phase (i.e., ovulation) when E2 was elevated. Results showed that the disinhibiting effect of alcohol increased nearly twofold during the late follicular phase when E2 was elevated. These findings highlight the role of alcohol-induced disinhibition as a potential behavioral mechanism by which fluctuations in ovarian hormones as a function of the menstrual cycle contribute to increased risk for excessive alcohol use in women. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Social Contact Reinforces Cocaine Self-Administration in Young Adult Male Rats: The Role of Social Reinforcement in Vulnerability to Drug Use.

Drug-using peers are recognized as a leading factor influencing drug use among adolescents and young adults. One mechanism by which peers influence drug use is by providing social reinforcement for using drugs. Social reinforcement may be provided in multiple ways, including by making social contact contingent on drug use (i.e., an individual must use drugs to gain/maintain access to a peer). The purpose of this study was to develop a preclinical model in which intravenous cocaine self-administration was positively reinforced by access to a social partner. Young adult male rats were trained to self-administer cocaine in operant conditioning chambers with a guillotine door that could be opened to an adjacent compartment housing either a social partner or a non-social stimulus. Once cocaine self-administration was established, the guillotine door was activated, and cocaine intake was reinforced by brief access to either a social (age- and sex-matched peer) or non-social (black-and-white athletic sock) stimulus. Contingent access to a social partner rapidly increased cocaine self-administration. Total cocaine intake was 2- to 3-fold greater in rats assigned to the social versus non-social condition across a 100-fold dose range. Cocaine intake rapidly increased when rats in the original non-social group were later provided with social partners, whereas cocaine intake resisted change and remained elevated when rats in the original social group had their partners removed. These data indicate that contingent access to a social partner increases drug intake and suggest that social reinforcement may represent a vulnerability factor that is particularly resistant to psychosocial interventions.

Interactions Between Opioids and Dextroamphetamine on Locomotor Activity: Influence of an Opioid's Relative Efficacy at the Mu Receptor.

Opioids and stimulants are often used in combination for both recreational and non-recreational purposes. High-efficacy mu opioid agonists generally increase the behavioral effects of stimulants, whereas opioid receptor antagonists generally attenuate the behavioral effects of stimulants; however, less is known regarding the interactions between stimulants and opioids possessing low to intermediate efficacy at the mu receptor. The purpose of this study was to examine the role of an opioid's relative efficacy at the mu receptor in altering the behavioral effects of dextro(d-)amphetamine. To this end, opioids possessing a range of relative efficacy at the mu receptor were examined alone and in combination with cumulative doses of d-amphetamine on a test of open-field, locomotor activity in male rats. Levorphanol, buprenorphine, butorphanol, nalbuphine, (-)-pentazocine, (-)-metazocine, (-)-cyclazocine, (-)-NANM, and nalorphine increased the locomotor effects of d-amphetamine in either an additive or greater-than-additive manner according to an effect-additive model. Only the selective, high-efficacy kappa agonist, spiradoline, and the non-selective opioid receptor antagonist, naloxone, failed to increase the effects of d-amphetamine under the conditions examined. These data indicate that opioids possessing a large range of relative efficacy at the mu receptor, including those possessing very low relative efficacy, significantly increase the locomotor effects of d-amphetamine.