Facilitation of Affiliation and Pair-Bond Formation by Vasopressin Receptor Gene Transfer into the Ventral Forebrain of a Monogamous Vole

Behaviors associated with monogamy, including pair-bond formation, are facilitated by the neuropeptide vasopressin and are prevented by a vasopressin receptor [V1a receptor (V1aR)] antagonist in the male prairie vole. The neuroanatomical distribution of V1aR dramatically differs between monogamous and nonmonogamous species. V1aR binding is denser in the ventral pallidal region of several unrelated monogamous species compared with nonmonogamous species. Because the ventral pallidum is involved in reinforcement and addiction, we hypothesize that V1aR activation in this region promotes pair-bond formation via a mechanism similar to conditioning. Using an adeno-associated viral vector to deliver the V1aR gene, we increased the density of V1aR binding in the ventral pallial region of male prairie voles. These males exhibited increased levels of both anxiety and affiliative behavior compared with control males. In addition, males overexpressing the V1aR in the ventral pallidal region, but not control males, formed strong partner preferences after an overnight cohabitation, without mating, with a female. These data demonstrate a role for ventral pallidal V1aR in affiliation and social attachment and provide a potential molecular mechanism for species differences in social organization.

[1]  T. Insel,et al.  Cellular Mechanisms of Social Attachment , 2001, Hormones and Behavior.

[2]  R. Samulski,et al.  Selective and rapid uptake of adeno-associated virus type 2 in brain. , 1998, Human gene therapy.

[3]  A. Deutch,et al.  Topography and functional role of dopaminergic projections from the ventral mesencephalic tegmentum to the ventral pallidum , 1992, Neuroscience.

[4]  Z. Wang,et al.  Vasopressin in the lateral septum regulates pair bond formation in male prairie voles (Microtus ochrogaster). , 2001, Behavioral neuroscience.

[5]  Thomas R. Insel,et al.  A role for central vasopressin in pair bonding in monogamous prairie voles , 1993, Nature.

[6]  T. Insel,et al.  Oxytocin Receptor Distribution Reflects Social Organization in Monogamous and Polygamous Voles , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[7]  T. Insel,et al.  The neurobiology of attachment , 2001, Nature Reviews Neuroscience.

[8]  S. Ikemoto,et al.  Localization of brain reinforcement mechanisms: intracranial self-administration and intracranial place-conditioning studies , 1999, Behavioural Brain Research.

[9]  S. Checkley,et al.  Changes in oxytocin and vasopressin secretion during sexual activity in men. , 1987, The Journal of clinical endocrinology and metabolism.

[10]  Carol Carter Porges.  Neuroendocrine perspectives on social attachment and love , 1998 .

[11]  A. Watson,et al.  A new linear V1A vasopressin antagonist and its use in characterizing receptor/G protein interactions. , 1997, Molecular pharmacology.

[12]  Young,et al.  Localization of Vasopressin (V1a) Receptor Binding and mRNA in the Rhesus Monkey Brain , 1999, Journal of neuroendocrinology.

[13]  C. Ferris,et al.  Patterns of brain vasopressin receptor distribution associated with social organization in microtine rodents , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[14]  T R Insel,et al.  A gender-specific mechanism for pair bonding: oxytocin and partner preference formation in monogamous voles. , 1995, Behavioral neuroscience.

[15]  F. Holsboer,et al.  Release of Vasopressin within the Rat Paraventricular Nucleus in Response to Emotional Stress: A Novel Mechanism of Regulating Adrenocorticotropic Hormone Secretion? , 1996, The Journal of Neuroscience.

[16]  L. Young,et al.  Species Differences in Paternal Behavior and Aggression in Peromyscus and Their Associations with Vasopressin Immunoreactivity and Receptors , 1999, Hormones and Behavior.

[17]  L. Young.  Oxytocin and Vasopressin Receptors and Species-Typical Social Behaviors , 1999, Hormones and Behavior.

[18]  T. Insel,et al.  Dopamine D2 receptors in the nucleus accumbens are important for social attachment in female prairie voles (Microtus ochrogaster). , 2000, Behavioral neuroscience.

[19]  C. T. Wotjak,et al.  Dissociated central and peripheral release of vasopressin, but not oxytocin, in response to repeated swim stress: New insights into the secretory capacities of peptidergic neurons , 1998, Neuroscience.

[20]  T. Insel,et al.  Increased affiliative response to vasopressin in mice expressing the V1a receptor from a monogamous vole , 1999, Nature.

[21]  T. Insel,et al.  Species differences in V1a receptor gene expression in monogamous and nonmonogamous voles: behavioral consequences. , 1997, Behavioral neuroscience.

[22]  C. Wotjak,et al.  Septal vasopressin modulates anxiety-related behaviour in rats , 1996, Neuroscience Letters.

[23]  D. Dewsbury,et al.  Differences in affiliative behavior, pair bonding, and vaginal cytology in two species of vole (Microtus ochrogaster and M. montanus). , 1990, Journal of comparative psychology.

[24]  R. Buijs,et al.  The origin of the vasopressinergic and oxytocinergic innervation of the rat brain with special reference to the lateral septum , 1983, Brain Research.

[25]  T. Insel,et al.  Neuroendocrine bases of monogamy , 1998, Trends in Neurosciences.

[26]  E. Terwilliger,et al.  Adeno-Associated Virus Vector-Mediated Transgene Integration into Neurons and Other Nondividing Cell Targets , 1998, Journal of Virology.

[27]  P. Reier,et al.  Efficient transduction of green fluorescent protein in spinal cord neurons using adeno-associated virus vectors containing cell type-specific promoters , 1997, Gene Therapy.

[28]  C. Carter,et al.  The effects of oxytocin and vasopressin on partner preferences in male and female prairie voles (Microtus ochrogaster). , 1999, Behavioral neuroscience.

[29]  S. Zeki,et al.  The neural basis of romantic love , 2000, Neuroreport.

[30]  Joseph B. Justice,et al.  Conditioned place preference and locomotor activation produced by injection of psychostimulants into ventral pallidum , 1996, Brain Research.

[31]  Carter Cs,et al.  Monogamy and the prairie vole. , 1993, Scientific American.

[32]  P. Sternweis,et al.  Photoaffinity labeling of two rat liver plasma membrane proteins with [32P]gamma-azidoanilido GTP in response to vasopressin. Immunologic identification as alpha subunits of the Gq class of G proteins. , 1991, The Journal of biological chemistry.

[33]  T. Insel,et al.  Mating in the monogamous male: Behavioral consequences , 1995, Physiology & Behavior.

[34]  T. Insel,et al.  Immunoreactivity of central vasopressin and oxytocin pathways in microtine rodents: A quantitative comparative study , 1996, The Journal of comparative neurology.

[35]  L. Getz,et al.  Monogamy and the prairie vole. , 1993, Scientific American.

[36]  F. Holsboer,et al.  V1 vasopressin receptor antisense oligodeoxynucleotide into septum reduces vasopressin binding, social discrimination abilities, and anxiety-related behavior in rats , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.