Transient inactivation of the ventral tegmental area selectively disrupts the expression of conditioned place preference for pup- but not cocaine-paired contexts

Abstract

The ventral tegmental area (VTA) plays a critical role in motivated behavior. However, it remains unclear whether intact VTA function is necessary for motivated behavior to seek contexts repeatedly paired with natural stimuli and/or pharmacological stimuli. In the present study, conditioned place preference (CPP) was induced with highly salient natural or drug stimuli attributed with strong incentive-motivational value in each of 2 female models: Postpartum females were conditioned to associate one unique context in the CPP apparatus with young offspring (pups) and a second context with a neutral stimulus, and virgin females were conditioned to associate unique contexts with cocaine (5 mg/kg ip) and saline injections. Immediately before CPP testing, each female received a microinfusion of bupivacaine bilaterally into the VTA to transiently inactivate the region; subjects were also tested after saline microinfusion into the VTA. Postpartum females' preference for the pup-paired context was abolished by VTA inactivation but was restored to high control levels after saline microinfusion. In separate tests, VTA inactivation also reduced motivated pup licking and pup retrieval in postpartum females, suggesting that intact VTA function is required for the expression of both pup CPP and motivated pup-directed behaviors. Cocaine CPP remained unaffected by VTA inactivation. Locomotion was not affected by VTA microinfusions but was severely impaired by bupivacaine microinfusions into the substantia nigra. We concluded that the VTA is differentially involved in the expression of conditioned preference for contexts paired with pups, a salient natural stimulus, and contexts paired with cocaine.

Figure 1

Histology. The placement of injector tips of bilateral cannulae in individual virgin (a) and postpartum (b) females with cannulae aimed at the ventral tegmental area (i.e., VTA females) or control females with cannulae aimed at the substantia nigra (Substantial Nigra controls; c), dorsally/rostrally to the VTA (i.e., Injection controls; d), and that had unmovable stylets (i.e., Surgical controls; e). Approximate stereotaxic coordinates, represented as millimeters posterior to Bregma, are listed to the right.

Figure 2

Conditioned preferences (a) and times (b) for each stimulus-paired context following bupivacaine (striped bars) and saline microinfusions (solid bars) in Injection controls, in which cannulae terminated dorsally/rostrally to the ventral tegmental area.

Figure 3

Mean time (min) spent in each stimulus-paired context of the place preference apparatus during the pre-conditioning session by virgin (a) and postpartum (b) females. P<0.05 for all within-groups (*) comparisons.

Figure 4

Individual preferences for each stimulus-paired context (a) and mean time (min) spent in each stimulus-paired context (b) during the post-conditioning test session(s) by postpartum females. Immediately prior to the start of the test session, females were given an intra-VTA microinjection containing 2% bupivacaine (striped bars) or saline solution (solid bars); all control females were handled but no microinjections were administered (open bars). All between-groups (#) and within-groups (*) comparisons, P<0.05.

Figure 5

Individual preferences for each stimulus-paired context (a) and mean time (min) spent in each stimulus-paired context (b) during the post-conditioning test session(s) by virgin females. Immediately prior to the start of the test session, females were given an intra-VTA microinjection containing 2% bupivacaine (striped bars) or saline solution (solid bars); all control females were handled but no microinjections were administered (open bars).

Figure 6

Mean locomotor rate (beam breaks per second) of females across the post-conditioning test session, immediately following intra-VTA microinfusions of 2% bupivacaine (open circles) or saline (filled circles). Locomotor rates of postpartum females in the pup-paired (a) and empty (b) contexts and of virgin females in the cocaine-paired (c) and saline-paired (d) contexts are shown. Inset: Mean locomotor rate in each CPP chamber pooled across entire 60min session following intra-VTA microinfusions of bupivacaine (striped bars) or saline (solid bars).

Figure 7

Mean latency to perform (a) and number of observations of (b) various maternal behaviors by postpartum females, immediately following intra-VTA microinfusions of 2% bupivacaine (striped bars) or saline (solid bars). Intact females were handled but no microinjections were administered (open bars). All between-groups (#) and within-groups (*) comparisons, P<0.05.