Dopamine D1 versus D4 Receptors Differentially Modulate the Encoding of Salient versus Nonsalient Emotional Information in the Medial Prefrontal Cortex

Dopamine (DA) transmission plays a critical role in the processing of emotionally salient information and in associative learning and memory processes. Within the mammalian brain, neurons within the medial prefrontal cortex (mPFC) are involved critically in the encoding, expression, and extinction of emotionally salient learned information. Within the mPFC, dopaminergic transmission is involved importantly in controlling attentional and motivational processes, particularly within the context of emotionally salient sensory information. Considerable evidence suggests differential roles for DAD(1)-like versus D-2-like receptors, including the D-4 receptor subtype, in the regulation of neuronal activity and emotional processing within the mPFC. Using an olfactory fear-conditioning assay in rats, we compared the roles of DA D-1 versus D-4 receptor activation during the encoding and recall phases of emotional learning and memory. We report that specific activation of DA D-4 receptors within the mPFC strongly potentiates the salience of normally nonsalient emotional associative fear memories and blocks the encoding of suprathreshold conditioned fear associations. However, D-4 receptor activation has no effect on the recall of previously learned emotionally salient conditioned memories. In contrast, intra-mPFC D-1 receptor activation failed to increase the emotional salience of subthreshold fear stimuli but completely blocked the expression of previously learned emotionally relevant information, demonstrating that DA D-4 versus D-1 subtype receptor transmission within the mPFC plays distinct functional roles in the processing of emotionally salient versus nonsalient associative information and differentially modulates the encoding versus recall phases of emotional memory within the mPFC.