Lactation provides a rewarding experience beneficial to mother-infant bonding. Cocaine addiction can sever this critical mother-infant experience, possibly affecting child psychosocial development. The main hypothesis of the proposed research is that adaptations in mesocortical dopamine function, long after chronic cocaine administration, affect maternal responsiveness to newborns. Functional MRI, in vivo microdialysis and autoradiographic methods will be employed to identify neural networks activated by suckling, a natural reward in lactating rats.
Two specific aims are proposed. 1) It is hypothesized that the medial prefrontal cortex (mPFC) of cocaine sensitized dams is less responsive to suckling but will be activated by distal presentation of pups (supporting a greater appetitive drive). To test this, the neural response to distal presentation of pups or suckling stimulation is imaged in drug naive and cocaine sensitized dams. During imaging sessions, pups are housed in a special cradle that controls access to nipples or a clear plastic vivarium that simulates the maternal home cage. These data will be complemented by experiments testing for appetitive and consummately components of maternal behaviors in control and cocaine sensitized mothers. Alterations in response to suckling pups or pup cues will be accompanied by increased dopamine (DA) transporter (DAT) function with concomitant changes in extracellular DA and its receptors in the mPFC. 2) It is hypothesized that the appetitive and consummatory components of maternal responding are modulated by dopamine signaling mechanisms in the mPFC. To test this, cocaine sensitized and control mothers are given an intra-mPFC D1-, D2-like DA receptor or DAT blocker and appetitive and consummatory maternal responses analyzed.
In specific aim 2, DAT binding and D1 and D2 receptor density will be assessed in brain tissue slices and mPFC DA levels measured in response to suckling pups. The studies in Specific Aim 2 will also examine DA function in the nucleus accumbens, a brain area associated, with reward seeking behavior. By understanding the neural mechanisms underlying maternal behaviors and the role of mPFC DA in the expression of these behaviors, it will be possible to target brain substrates for clinical intervention in mothers recovering from cocaine addiction.
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