During the past decade, there has been increased attention upon hormonal involvement in drug abuse. These studies have been motivated by the increased number of women addicted to psychostimulants, which has become a growing public health concern. Furthermore, compelling data indicate the existence of a role for ovarian hormones in drug addiction. Men and women addicted to cocaine display distinct profiles in incidence, onset, and progression of addiction, in addition to their response to treatment (Adinoff et al., 2003
). Preclinical and clinical studies have demonstrated that there are sex-specific differences in the biological response to cocaine, as well as to other stimulants. While there are some differences among specific classes of abused drugs, the general pattern of sex differences is the same for all drugs of abuse (Becker and Hu, 2008
Understanding the neurobiological substrates involved in drug-taking behavior is a central challenge in addiction research. Neuroimaging has contributed substantial insight into this issue, as well as into the neurobiological basis for sex differences, but it has been less applied to questions of sex differences in drug abuse. The studies reviewed hererin suggest a complex influence and interplay between sex differences and drug abuse. PET, SPECT, and fMRI all point to differences in activation of the amygdala, insula, cingulate cortex, and frontal cortex between male and female cocaine users, as well as distinct changes in resting state between the sexes. These changes may be related to greater DAT availability in women as well as less susceptibility to drug-induced neuronal damage.
Neuroimaging offers the unique ability to investigate sex differences in the composition, development, and function of brains of current drug users over time. Furthermore, multiple imaging techniques can be used to address the questions of where and how these sex differences come into play. Parallel studies in animals and human subjects should be able to provide a powerful translational approach, allowing phenomena observed in humans to be investigated in animals, and then translated back into treatment strategies and approaches. In particular, animal models offer the opportunity for longitudinal designs in order to address neurobiological mechanisms underlying chronic cocaine use. Imaging techniques such as PET can help identify target brain structures and receptors in both the male and female brains. Furthermore, neuroimaging should be applied to understanding the developmental differences in anatomy between the sexes, how these differences interact with cocaine use, and how cocaine use differentially affects brain activation, connectivity, and receptor regulation between males and females.
Overall, there is an obvious lack of animal neuroimaging studies addressing the role of sexes in drug abuse. Animal models offer the ability to tightly control and design experiments to address complicated questions in a systematic, thorough manner, and have the potential to answer many questions when combined with the versatility of neuroimaging techniques. For instance, a set of longitudinal neuroimaging studies across the life-span in animals of both sexes to verify whether hormones exert a role in the predisposition to, acquisition of, and maintenance of cocaine use would prove most interesting and informative. Furthermore, such studies could illuminate the role of sex hormones in the neural adaptations caused by cocaine use.
In order to apply these powerful imaging techniques to determining the role of hormones in sex-specific differences in drug abuse, additional measures and controls, such as hormonal assays, are still required to aid interpretation of the results. There is a strong need for further studies investigating sex differences in both animals under carefully controlled conditions and in drug abusers. Reliable radiotracers for dopaminergic targets have been developed and should be utilized to map out any baseline differences between males and females in dopaminergic receptor and transporter distributions and densities, as well as different metabolic responses to initial and prolonged cocaine exposure, and any changes in dopaminergic structure than may differ between males and females following stabilization of cocaine use. These studies would help guide individual treatment strategies that could target the particular neurobiology of cocaine abuse in women.