The medial preoptic area is necessary for motivated choice of pup- over cocaine-associated environments by early postpartum rats

Abstract

Converging evidence suggests that the motivation to seek cocaine during the postpartum period is significantly impacted by the competing incentives of offspring, a stimulus unique to this life stage. In the present study, the functional role of the medial preoptic area (mPOA), a critical site involved in maternal responsiveness, on processing incentive value of pup-associated cues and influencing response allocation for pup- over cocaine-associated environments was investigated using a concurrent pup/cocaine choice conditioned place preference (CPP) paradigm. Early postpartum females with bilateral guide cannulae aimed into the mPOA or into anatomical control sites were conditioned, from postpartum days (PPD) 4 to 7, to associate different uniquely featured environments with pups or cocaine. CPP was tested on PPD8 following intra-mPOA infusions of either 2% bupivacaine or saline vehicle. In two additional experiments, the effects of intra-mPOA infusions of bupivacaine on expression of conditioned responding induced by environments associated with either pups or cocaine were examined separately. Transient inactivation of the mPOA selectively blocked the conditioned preferences for pup-associated environments, significantly contrasting the robust pup-CPP found in non-surgical and intra-mPOA vehicle-treated females. In contrast, mPOA inactivation failed to alter cocaine-CPP in postpartum females. When given a choice between environments associated with pups or cocaine, transient functional inactivation of the mPOA altered choice behavior, biasing the preference of females toward cocaine-associated environments, such that almost all preferred cocaine- and none the pup-associated option. The anatomical specificity was revealed when inactivation of adjacent regions to the mPOA did not affect CPP responses for pups. The findings support a critical role for the mPOA in mediating pup-seeking behavior, and further suggest that the competing properties of pups over alternative incentives, including drugs of abuse, rely on mPOA integrity to provide relevant pup-related information to the circuitry underlying the choice behavior between pups and alternative stimuli.

Figure 1

Comparison of the conditioned response of postpartum females to an environment associated with either 1.0 or 5.0 mg/kg IP cocaine versus one associated with saline or pups. (A) Conditioned chamber preferences and (B) mean time spent in each chamber of the apparatus during the cocaine-CPP test session, after conditioning with IP injections of either 1.0 or 5.0 mg/kg cocaine and saline. (C) Conditioned chamber preferences and (D) mean time spent in each chamber of the apparatus during the concurrent pup/cocaine-CPP test session, after conditioning with IP cocaine injections (either 1.0 or 5.0 mg/kg) and maternal interaction with pups.

Figure 2

Effect of transient inactivation of the mPOA on expression of pup-induced CPP. (A) Schematic representation, based on the microscopic analysis of cresyl violet-stained sections, of mPOA and dorsal control sites for all rats receiving infusion treatments. Circles represent the most ventral extent of the injector tracks in the brain. Plates were taken from the atlas of Paxinos and Watson (1997). Numbers beside each plate indicate the distance caudal to bregma in millimeters. (B) Pup-associated chamber preferences and times during the pre- and postconditioning sessions. (C) Conditioned chamber preferences and (D) mean time spent in each chamber of the CPP apparatus during the test session by non-surgical control (n=10), dorsal bupivacaine-treated (n=7), mPOA bupivacaine-treated (n=10), and mPOA vehicle-treated (n=9) postpartum females. * denotes significant differences between groups, and ^# indicates significant within-group differences in pre- vs. postconditioning responding; all P<0.05.

Figure 3

Effect of transient inactivation of the mPOA on expression of cocaine-induced CPP. (A) Schematic representation, based on the microscopic analysis of cresyl violet-stained sections, of injection sites for all rats receiving infusion treatments. (B) Cocaine-associated chamber preferences and times during the pre- and postconditioning sessions. (C) Conditioned chamber preferences and (D) mean time spent in each chamber of the CPP apparatus by non-surgical control females (n=12), and mPOA cannulated females (n=12) following either vehicle or inactivation treatment with 2% bupivacaine. * denotes significant differences between groups, and ^# indicates significant within-group differences in pre- vs. postconditioning responding; all P<0.05.

Figure 4

Effect of transient mPOA inactivation on motivated choice of pup- versus cocaine-associated environments in a concurrent pup/cocaine-CPP. (A) Schematic representation, based on the microscopic analysis of cresyl violet-stained sections, of injection sites for all rats receiving infusion treatments. (B) Chamber preferences and times during the pre- and postconditioning sessions for the subset of females that exhibited a conditioned preference for either pup- or cocaine-associated environments. (C) Conditioned chamber preferences and (D) mean time spent in each chamber of the CPP apparatus during the test session by non-surgical control (n=10), mPOA bupivacaine-treated (n=9), and mPOA vehicle-treated (n=8) postpartum females. *denotes significant differences between groups, and ^# indicates significant within-group differences in pre- vs. postconditioning responding; all P<0.05.