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Development of cocaine sensitization before pregnancy affects subsequent maternal retrieval of pups and prefrontal cortical activity during nursing.

ABSTRACT: Pups are a highly rewarding stimulus for early postpartum rats. Our previous work supports this notion by showing that suckling activates the mesocorticolimbic system in mothers. In the present study, we tested whether development of behavioral sensitization to cocaine before pregnancy affects the neural response to pups during the early postpartum days (PD). Virgin rats were repeatedly administered cocaine for 14 days (15 mg kg(-1)) and withdrawn from treatment during breeding and pregnancy. The neural response to suckling was measured at PD 4-8 using blood-oxygen-level-dependent (BOLD) MRI or microdialysis. Our results show that BOLD activation in the medial prefrontal cortex (PFC), septum and auditory cortex was curtailed in cocaine-sensitized dams. No differences between cocaine sensitized and saline control dams were observed in the nucleus accumbens, olfactory structures, or in 48 additional major brain regions that were analyzed. Baseline, but not pup-stimulated, dopamine (DA) levels in the medial PFC were lower in cocaine-sensitized dams than in controls. When tested for maternal behaviors, cocaine-sensitized dams showed significantly faster retrieval of pups without changes in other maternal behaviors such as grouping, crouching and defending the nest. Taken together, the present findings suggest that maternal motivation to retrieve pups was enhanced by repeated cocaine exposure and withdrawal, a result reminiscent of 'cross-sensitization' between the drug and a natural reward. Changes in retrieval behavior in cocaine-sensitized mothers might be associated with a hypo-responsive medial PFC.

SUBMITTER: Febo M

PROVIDER: S-EPMC2220157 | biostudies-literature | 2007 Aug

REPOSITORIES: biostudies-literature

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Development of cocaine sensitization before pregnancy affects subsequent maternal retrieval of pups and prefrontal cortical activity during nursing.

Febo M M Ferris C F CF

Neuroscience 20070725 2

Pups are a highly rewarding stimulus for early postpartum rats. Our previous work supports this notion by showing that suckling activates the mesocorticolimbic system in mothers. In the present study, we tested whether development of behavioral sensitization to cocaine before pregnancy affects the neural response to pups during the early postpartum days (PD). Virgin rats were repeatedly administered cocaine for 14 days (15 mg kg(-1)) and withdrawn from treatment during breeding and pregnancy. Th ...[more]

PMID: 17651902

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Project description:Presentation of drug-associated cues provokes craving and drug seeking, and elimination of these associative memories would facilitate recovery from addiction. Emotionally salient memories are maintained during retrieval, as particular pharmacologic or optogenetic perturbations of memory circuits during retrieval, but not after, can induce long-lasting memory impairments. For example, in rats, inhibition of noradrenergic beta-receptors, which control intrinsic neuronal excitability, in the prelimbic medial prefrontal cortex (PL-mPFC) can cause long-term memory impairments that prevent subsequent cocaine-induced reinstatement. The physiologic mechanisms that allow noradrenergic signaling to maintain drug-associated memories during retrieval, however, are unclear. Here we combine patch-clamp electrophysiology ex vivo and behavioral neuropharmacology in vivo to evaluate the mechanisms that maintain drug-associated memory during retrieval in rats. Consistent with previous studies, we find that cocaine experience increases the intrinsic excitability of pyramidal neurons in PL-mPFC. In addition, we now find that this intrinsic plasticity positively predicts the retrieval of a cocaine-induced conditioned place preference (CPP) memory, suggesting that such plasticity may contribute to drug-associated memory retrieval. In further support of this, we find that pharmacological blockade of a cAMP-dependent signaling cascade, which allows noradrenergic signaling to elevate neuronal excitability, is required for memory maintenance during retrieval. Thus, inhibition of PL-mPFC neuronal excitability during memory retrieval not only leads to long-term deficits in the memory, but this memory deficit provides protection against subsequent cocaine-induced reinstatement. These data reveal that PL-mPFC intrinsic neuronal excitability maintains a cocaine-associated memory during retrieval and suggest a unique mechanism whereby drug-associated memories could be targeted for elimination.

Dataset Information

Development of cocaine sensitization before pregnancy affects subsequent maternal retrieval of pups and prefrontal cortical activity during nursing.

Publications

Development of cocaine sensitization before pregnancy affects subsequent maternal retrieval of pups and prefrontal cortical activity during nursing.

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