Dr. Zuoxin Wang

Research Interest

Neurobiology of Social Attachment

The major emphasis of our research has been the neurobiology of social attachment in mammals. Sexual attraction and the selective social attachments that often follow are two of the most powerful driving forces of human behavior. There is little doubt that the ability to form intense social attachments - or pair bonds - with a mate has a biological architecture with definable molecular and neural mechanisms. Our laboratory uses the monogamous prairie vole (Microtus ochrogaster) as a model system to study the neuronal and hormonal mechanisms underlying social attachment because this rodent species exhibits high levels of mating-induced pair bonding. Our earlier work, along with the work of others, demonstrated that the neuropeptides vasopressin and oxytocin in particular brain areas play important roles in pair bond formation of male and female prairie voles. Our recent work has been focused on dopamine, a neurochemical that is released during both natural and drug rewards and that plays an important role in learning and memory. We have demonstrated that dopamine is released during mating in the nucleus accumbens (NAcc), an area which contains dopamine terminals and different types of dopamine receptors in voles. We have shown that, in the NAcc, dopamine differentially mediates formation and maintenance of pair bonding behavior in a receptor-specific manner. Further, we have demonstrated that dopamine and oxytocin interact in NAcc in the regulation of pair bonding. Our current efforts are focused on the examination of intracellular mechanisms underlying receptor-specific dopamine effects and dopamine interactions with oxytocin/vasopressin in the regulation of pair bonding.

Environmental and Hormonal Regulation of Adult Neurogenesis

Although recent studies have amply demonstrated that neurogenesis occurs continuously throughout life in certain brain areas of adult vertebrates, including rodents, non-human primates, and humans, the factors that influence and are functionally important for this process remain largely unexplored. Because manipulations of the social environment have profound effects on physiology and behaviors of the prairie vole, we have used this model system to study the effects of environmental and hormonal manipulation on adult neurogenesis. We have demonstrated that in female prairie voles, mating and experience with a male facilitate, whereas social isolation inhibits, neurogenesis in selected brain areas. We have also found that the gonadal steroid hormone, estrogen, differently regulates neurogenesis in selected brain areas of females between monogamous and non-monogamous voles. Further, in male voles, we have found that gonadal steroid hormones, including testosterone and estrogen, may act on estrogen-receptor mediated mechanisms in the regulation of locally proliferated cells in the amygdala - a brain area implicated in social behaviors. Our current efforts are focused on the interactions between gonadal steroid hormones and other neurochemicals in the regulation of adult neurogenesis, and on the functional significance of new neurons in social behaviors.

Social and Drug Reward Interactions and Underlying Mechanisms

Our newest line of research is to develop the prairie vole model for the study of social and drug reward interactions and their underlying mechanisms. As noted above, we have demonstrated that NAcc dopamine regulates prairie vole pair bonding behavior. Interestingly, dopamine regulation of pair bonding appears to be very similar to dopamine regulation of drug seeking behavior. Because pair bonding and drug reward are regulated by very similar neural mechanisms, and because both result in enduring changes in behavior, we hypothesized that addiction to drugs of abuse and pair bonding may act on the same brain-reward circuitry, and that the two may interact with each other. The prairie vole is the perfect animal model to test this hypothesis. Our recent data have shown that prairie voles display amphetamine-induced conditioned place preferences (CPP), suggesting that amphetamine is rewarding in voles as in other species of rodents. Our current efforts are focused on examining changes in brain-reward dopamine circuitry after amphetamine treatment, and on comparing such changes with those induced by pair bonding.

Current Research

• Receptor-specific mechanisms underlying dopamine regulation of pair bonding
• Neurochemical interactions in the regulation of pair bonding behavior
• Social environment and gonadal steroid regulation of adult neurogenesis in voles
• Amphetamine, dopamine, and conditioned place preference in voles
• Dopamine regulation of social and drug reward interactions

Publications

• Fowler CF, Liu Y, and Wang ZX. Estrogen and adult neurogenesis in the amygdala and hypothalamus. Brain Res Rev. 57:342-351. (2008) PDF
• Young KL, Liu Y, and Wang ZX. Neurobiology of social attachment: a comparative approach to behavioral, neuroanatomical, and neurochemical studies. Comp Biochem Physiol. Part C 148:401-410. (2008) PDF
• Aragona BJ and Wang ZX. Opposing regulation of pair bond formation by cAMP signaling within the nucleus accumbens shell. J Neurosci. 27:13352-13356. (2007) PDF
• Curtis JT and Wang ZX. Amphetamine effects in microtine rodents: a comparative study using monogamous and promiscuous vole species. Neuroscience. 148:857-866. (2007) PDF
• Gobrogge KL, Liu Y, Jia X and Wang ZX. Anterior hypothalamic neural activation and neurochemical association with aggression in pair bonded male prairie voles. J Comp Neurol. 502:1109-1122. (2007) PDF
• Aragona BJ, Detwiler JM, and Wang ZX. Amphetamine reward in the monogamous prairie vole. Neurosci Lett. 418:190-194. (2007) PDF
• Aragona BJ, Liu Y, Yu J, Curtis TJ, Detwiler J, Insel TR and Wang ZX. Nucleus accumbens dopamine differentially mediates formation and maintenance of monogamous pair bonds. Nature Neurosci. 9:133-139. (2006) PDF
• Smeltzer M, Curtis TJ, Aragona BJ, and Wang ZX. Vasopressin, oxytocin, and dopamine receptors in the prefrontal cortex of monogamous and promiscuous voles. Neurosci Lett. 394:146-151. (2006) PDF
• Curtis JT and Wang ZX. Ventral tegmental area involvement in pair bonding in male prairie voles. Physiol Behav. 86:338-346. (2005)
• Stowe JR, Liu Y, Curtis TJ, Freeman ME, and Wang ZX. Species differences in anxiety-related responses in male prairie and meadow voles: the effects of social isolation. Physiol Behav. 86:369-378. (2005)
• Curtis JT and Wang ZX. Glucocorticoid receptor involvement in pair bonding in female prairie voles: The effects of acute blockade and interactions with central dopamine reward systems. Neuroscience. 134:369-76. (2005)
• Fowler CD, Johnson F, and Wang ZX. Estrogen regulation of cell proliferation and distribution of estrogen receptor-alpha in the brains of adult female prairie and meadow voles. J Comp Neurol. 489:166-179. (2005)
• Young LJ and Wang ZX. The neurobiology of pair bonding. Nature Neurosci. 7:1048-1054. (2004)
• Liu Y and Wang ZX. Nucleus accumbens oxytocin and dopamine interact to regulate pair bond formation in female prairie voles. Neuroscience. 121:537-544. (2003)
• Fowler CD, Freeman ME, and Wang ZX. Newly proliferated cells in the adult male amygdala are affected by gonadal steroid hormones. J Neurobiol. 57:257-269. (2003)
• Curtis JT, Stowe J, and Wang ZX. Differential effects of intraspecific interactions on the striatal dopamine system in social and non-social voles. Neuroscience. 118:1165-1173. (2003)
• Aragona BJ, Liu Y, Curtis, TJ, Stephan FK, and Wang ZX. A critical role for nucleus accumbens dopamine in partner-preference formation in male prairie voles. J Neurosci. 23:3483-3490. (2003)