Preference for cocaine- versus pup-associated cues differentially activates neurons expressing either Fos or cocaine- and amphetamine-regulated transcript in lactating, maternal rodents.

We studied the neuronal basis of the motivational response to two powerful but radically different rewards-cocaine and maternal nurturing of pups in the postpartum rat (dam) which is in a unique motivational state. We used a place preference method designed to offer a choice between cues associated with a natural reinforcer (pups) and those associated with a pharmacologic reinforcer (cocaine). Using c-Fos or cocaine- and amphetamine-regulated transcript (CART) immunocytochemistry, we identified the neuronal groups that are activated when the dams expressed a preference for either cues-associated with pups or cues-associated with cocaine. Dams that preferred the cocaine-associated cues had more c-Fos positive neurons in medial prefrontal cortex, nucleus accumbens, and basolateral nucleus of amygdala than pup-associated cue preferring dams or control. Except for the accumbens, there was activation of neurons in these same regions with the pup-associated cue preference. In the nucleus accumbens only CART-immunoreactive (not c-Fos) neurons were activated with pup-cue preference. Notably, the medial preoptic area was the single area where greater activation of neurons was seen with a preference for pup-associated versus cocaine-associated cues. These responses were identified in the absence of the stimuli (cocaine or pups) and are proposed to be, in part, activation of these neurons related to motivational processing. Neither the distribution of neurons responding to pup-associated cue preference nor the demonstration that CART-expressing neurons are responsive to reward-associated cue preference has been previously reported. We hypothesize that the expression of preference for cocaine versus pup-associated cues is made possible by the concerted activity of these regionally distributed networks of neurons that are in part specific to the preference response.