A dopaminergic switch for fear to safety transitions

Overcoming aversive emotional memories requires neural systems that detect when fear responses are no longer appropriate. The midbrain ventral tegmental area (VTA) dopamine system has been implicated in reward and more broadly in signalling when a better than expected outcome has occurred. This suggests that it may be important in guiding fear to safety transitions. We report that when an expected aversive outcome does not occur, activity in midbrain dopamine neurons is necessary to extinguish behavioral fear responses and engage molecular signalling events in extinction learning circuits. Furthermore, a specific dopamine projection to the nucleus accumbens medial shell is partially responsible for this effect. By contrast, a separate dopamine projection to the medial prefrontal cortex opposes extinction learning. This demonstrates a novel function for the canonical VTA-dopamine reward system and reveals opposing behavioural roles for different dopamine neuron projections in fear extinction learning

Prior Cocaine Experience Impairs Normal Phasic Dopamine Signals of Reward Value in Accumbens Shell

Dopamine signals have repeatedly been linked to associative learning and motivational processes. However, there is considerably less agreement on a role for dopamine in reward processing, and therefore whether neuroplastic changes in dopamine function following chronic exposure to drugs of abuse such as cocaine may impair appropriate valuation of rewarding stimuli. To quantify this, we voltammetrically measured real-time dopamine release in the nucleus accumbens (NAc) core or shell while rats received unsignaled deliveries of either a small (1 pellet) or large (2 pellets) reward. In drug-naive controls, core dopamine signals did not discriminate between reward size at any point, while in the shell dopamine encoded magnitude differences only in a slower postpeak period. Despite this lack of discrimination between rewards by the peak DA response, controls easily discriminated between reward options in a subsequent choice task. In contrast, phasic dopamine reward signals were strongly altered by cocaine experience; core dopamine decreased peak response but increased discrimination between reward magnitudes while shell lost phasic responses to reward receipt altogether. Notably, animals with cocaine-associated alterations in dopamine signals for reward magnitude failed to subsequently discriminate between reward options. These findings suggest that cocaine self-administration alters the ability for dopamine signals to appropriately assign value to rewards and thus may in part contribute to later deficits in behaviors that depend on appropriate outcome valuation

Experimental Psychopharmacology

Studies of psychopharmacology in experimental animals are a major source of information on the effects that drugs elicit on superior brain functions. Moreover, studies of psychopharmacology are a key step in the refinement of existing drugs and development of new drugs for the treatment of psychiatric diseases, such as anxiety, depression, and psychosis. The present chapter provides an overview of the techniques and animal models that can be used in studies of experimental psychopharmacology and discusses their strengths and limitations