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.
Aragona BJ, Liu Y, Curtis, TJ, Stephan FK, and Wang ZX (2003) A critical
role for nucleus accumbens dopamine in partner-preference formation
in male prairie voles. J. Neurosci., 23:3483-3490. [pdf]
Curtis
JT, Stowe J, and Wang ZX (2003) Differential effects of intraspecific
interactions on the striatal dopamine system in social and non-social
voles. Neuroscience, 118:1165-1173. [pdf]
Fowler
CD, Freeman ME, and Wang ZX (2003) Newly proliferated cells in the
adult male amygdala are affected by gonadal steroid hormones. J.
Neurobiol., 57:257-269. [pdf]
Liu
Y and Wang ZX (2003) Nucleus accumbens oxytocin and dopamine interact
to regulate pair bond formation in female prairie voles. Neuroscience,
121:537-544. [pdf]
Young
LJ and Wang ZX (2004) The neurobiology of pair bonding. Nature
Neurosci., 7:1048-1054. [pdf]
Fowler
CD, Johnson F, and Wang ZX (2005) 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. [pdf]
Curtis
JT and Wang ZX (2005) 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. [pdf]
Stowe
JR, Liu Y, Curtis TJ, Freeman ME, and Wang ZX (2005) Species differences
in anxiety-related responses in male prairie and meadow voles: the
effects of social isolation. Physiol. Behav., 86:369-378. [pdf]
Curtis
JT and Wang ZX (2005) Ventral tegmental area involvement in pair bonding
in male prairie voles. Physiol. Behav., 86:338-346. [pdf]
Aragona
BJ, Liu Y, Yu J, Curtis TJ, Detwiler J, Insel TR and Wang ZX (2006)
Nucleus accumbens dopamine differentially mediates formation and maintenance
of monogamous pair bonds. Nature Neurosci., 9:133-139. [pdf]
Smeltzer M, Curtis TJ, Aragona BJ, and Wang ZX (2006) Vasopressin,
oxytocin, and dopamine receptors in the prefrontal cortex of monogamous
and promiscuous voles. Neurosci. Lett., 394:146-151. [pdf]
Aragona BJ, Detwiler JM, and Wang ZX (2007) Amphetamine reward in
the monogamous prairie vole. Neurosci. Lett., 418:190-194. [pdf]
Gobrogge KL, Liu Y, Jia X and Wang ZX (2007) Anterior hypothalamic
neural activation and neurochemical association with aggression in
pair bonded male prairie voles. J. Comp. Neurol., 502:1109-1122. [pdf]
Curtis JT and Wang ZX (2007) Amphetamine effects in microtine rodents:
a comparative study using monogamous and promiscuous vole species. Neuroscience, (in press). [pdf]
Fowler CF, Liu Y, and Wang ZX (in press) Estrogen and adult neurogenesis in the amygdala and hypothalamus. Brain Res. Rev. [pdf]
