The role of septal vasopressin innervation in paternal behavior in prairie voles (Microtus ochrogaster)

After being paired with females, male prairie voles show major changes in their social behaviors among which is an increase in paternal responsiveness. These changes are accompanied by fluctuations in the density of the [Argelvasopressin-immunoreactive (AVP-ir) fibers in the lateral septum, suggesting that septal AVP might be involved in these changes. To explore a possible involvement of septal AVP in paternal responsiveness, we tested whether injections of saline, AVP, or the Vla receptor antagonist [1-(,&mercaptogB,3-cyclopentamethylenepropionic acid),2-(O-methyltyrosine]AVP [d(CH2)sTyr(Me)AVP] into the lateral septum influenced the four most prominent paternal activities displayed by male prairie voles; grooming, crouching over, contacting, and retrieving pups. In a first experiment, sexually inexperienced males received a single injection of AVP, saline, or d(CH2)5Tyr(Me)AVP in the lateral septum, after which their paternal responsiveness was recorded during a 10-min period. AVP-injected animals spent more time contacting and crouching over pups, while d(CH2)sTyr(Me)AVP-injected animals spent less time grooming pups than saline-injected animals. In a follow-up study, one group of animals received an injection ofAVP preceded by an injection of saline or d(CH2)5Tyr(Me)AVP into the lateral septum. A second group of animals received an inijection of saline preceded by an injection of saline or d(CH2)sTyr(Me)AVP into the lateral septum. In both groups, animals spent less time grooming, crouching over, and contacting pups if they had first been injected with d(CH2)sTyr(Me)AVP. Control experiments suggested that the effects of AVP on paternal responsiveness were doseand site-specific. These data suggest that septal AVP enhances paternal responsiveness by a Via receptor-mediated mechanism. In monogamous rodent species, such as prairie voles (Microtus ochrogaster), males as well as females provide parental care (1). Although there is virtually no knowledge on the neural basis of parental behavior in prairie voles, there is much knowledge on the neural mechanisms underlying maternal behavior in other rodents, particularly in rats (2, 3). However, the neural mechanisms underlying paternal behavior are unknown. One study compared, but did not find differences in, central oxytocin binding sites between sexually naive and maternal prairie voles (4), although it did find an induction of oxytocin binding sites in maternal montane voles (Microtus montanus), a promiscuous species in which males do not provide paternal behavior (5). A recent comparison of prairie and meadow voles (Microtus pennsylvanicus) suggested that the [Arge]vasopressin-immunoreactive (AVP-ir) innervation of the lateral septum may be involved in paternal behavior. In meadow voles, another promiscuous species in which The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact. males do not provide paternal care (1, 6), the plexus ofAVP-ir fibers in the lateral septum did not differ between fathers and sexually inexperienced males, while in prairie voles, a monogamous species in which males do provide paternal care, this plexus was less dense in fathers than in sexually inexperienced males (7). A follow-up study showed that, compared with sexually inexperienced voles, the density of this plexus is dramatically lower in males that have been paired with females for 3 days (8), in which time they typically mate (9). After that, the density of the plexus returns to the levels of sexually inexperienced males, to drop again once the pups are born (8). Preliminary evidence suggests that this reduction in AVP-ir fiber density after mating is accompanied by an increase in AVP mRNA in the bed nucleus of the stria terminalis (10), the most likely source of these fibers, and therefore may reflect an increase in septal AVP release that is not immediately followed by a restoration of the AVP-ir content of the fibers (8). These fluctuations in AVP-ir fiber density might be related to changes in social behaviors. After mating, prairie voles develop a strong partner preference and increase their aggressiveness towards other conspecifics (11). A recent study showed that intraventricular injections of AVP enhanced these behaviors in males, whereas intraventricular injections of an AVP antagonist blocked mating-induced increases in these behaviors, suggesting that endogenous AVP release contributes to mating-induced behavioral changes (12). After mating, male prairie voles also show an increase in paternal responsiveness (8). Although there are no data on the effects of septal AVP injections on parental behavior, intracerebroventricular injections of AVP increase maternal responsiveness in rats (13). Therefore, the changes in the density of the AVP-ir fiber plexus after mating may also be related to the changes in paternal responsiveness. Here we test the hypothesis that septal AVP influences paternal responsiveness in male prairie voles. MATERIALS AND METHODS The subjects were sexually inexperienced male prairie voles from the F3/F4 generation of a breeding colony started with field-trapped animals. Twelve males were housed in pairs in plastic cages (44 x 24 x 20 cm) filled with peat, wood chips, and a 10-cm hay covering under a 14 hr/10 hr light/dark cycle at 21°C. When the animals were between 70 and 90 days old, 26-gauge stainless steel guide cannulas were implanted stereotaxically aimed at the lateral septum (nosebar at 0; 1.4mm rostral, 0.4mm unilateral, and 4 mm ventral to bregma) under ketamine anesthesia. Three days later, each subject received Abbreviations: AVP, [Arg8]vasopressin; AVP-ir, AVP-immunoreactive; BST, bed nucleus ofthe stria terminalis; MA, medial amygdaloid nucleus; d(CH2)5Tyr(Me)AVP, [1-(3-mercapto-pB,3-cyclopentamethylenepropionic acid),2-(O-methyl)tyrosine]AVP. § To whom reprint requests should be addressed.