These experiments focus on the neurobiological mediators of motivation to seek offspring versus cocaine during the postpartum period, a unique period in the life of the female, critical for the survival of her offspring. A foremost goal of my preclinical model is to explore the neural circuitry and neurochemistry supporting motivational responses in the postpartum female rat. I posit that these behavioral and neurobiological data will provide information that usefully generalizes to processes related to the human condition. These experiments will use conditioned place preference (CPP) as a measure of stimulus seeking because CPP does not require the presence of the stimulus during motivation testing, so the neural substrates active exclusively during seeking of the stimulus can be targeted.
Specific Aim Revealing the network of neurons and their neurotransmitters necessary for the choice of pup-associated versus cocaine-associated environments. A. Is the medial preoptic area (mPOA) necessary to determining the choice of environments associated with pups versus cocaine presented in a dual choice paradigm? I will test this using neuroanatomical site specific and transient inactivation (with bupivacaine a local anesthetic) of the mPOA during CPP test. B. Which additional components of the circuit are necessary to determining the choice of environments associated with pups versus cocaine presented in a dual choice paradigm? I will using methods used in the experiments in A, test the hypothesis that the ventral tegmental area, nucleus accumbens and the medial prefrontal cortex are necessary to the manifestation of CPP for either pup or cocaine-associated environments. C. What is the causal contribution of dopamine and glutamate mediated neurotransmission within key components of the neural circuit necessary for the choice of environments associated with pups versus cocaine? I will inject dopaminergic or glutametergic antagonists via site specifically directed cannulae into limited regions of this circuit at CPP test. It is likely that the incentive value and choice to seek each individual stimulus is established in a distributed neural network that underlies the components of motivated response, and that neuronal activation in this network is state-dependent, and that the postpartum state is a unique one that must be studied specifically. I posit that the different stimuli (pups versus cocaine) may recruit certain components of this network more strongly than others, providing a likely mechanism explaining why an individual attributes different incentive values to different stimuli. Exploring the specific circuitry mediating the choice between the two particular stimuli in my paradigm is likely to reveal neural substrate particular to this highly state dependent and functionally incompatible set of choices, seeking and caring for offspring or seeking cocaine.
Motivational forces at work in parents cause them to initiate care for their offspring. This is a vertebrate wide phenomena but strong motivation to seek and care for offspring is particularly common in mammals, including humans. However, a parent's world is full of choices. One choice that faces parents is the use of cocaine, which can have devastating consequences on parenting. These experiments examine how the motivation to seek cocaine might hijack the motivation to care for offspring using a well established laboratory model, the postpartum rat. Both the behavior of the rat, using a well established tool to measure motivation, the conditioned place preference procedure, and the brain structures that mediate choice behaviors will be endpoints of these experiments. These experiments will examine the behavioral neurobiology of a preclinical model which we fully expect will uncover principles of function that will generalize informatively to the human condition.
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