Distinct Role of Dopamine in the PFC and NAc During Exposure to Cocaine-Associated Cues

Abstract

Background Dopamine neurotransmission plays a critical role in reward in drug abuse and drug addiction. However, the role of dopamine in the recognition of drug-associated environmental stimuli, retrieval of drug-associated memory and drug-seeking behaviors is not fully understood. Methods Roles of dopamine neurotransmission in the prefrontal cortex (PFC) and nucleus accumbens (NAc) in the cocaine conditioned place preference (CPP) paradigm were evaluated using in vivo microdialysis. Results In mice that had acquired cocaine CPP, dopamine levels in the PFC, but not in the NAc, increased in response to cocaine-associated cues when mice were placed in the cocaine-chamber of an apparatus with two-separated chambers. The induction of the dopamine response and the development of cocaine CPP were mediated through activation of glutamate NMDA/AMPA receptor signaling in the PFC during conditioning. Activation of dopamine D1 or D2 receptor signaling in the PFC was required for cocaine-induced locomotion, but not for the induction of the dopamine response or the development of cocaine CPP. Interestingly, dopamine levels in the NAc increased in response to cocaine-associated cues when mice were placed at the center of an apparatus with two-connected chambers, which requires motivated exploration associated with cocaine reward. Conclusions Dopamine neurotransmission in the PFC is activated by the exposure to the cocaine-associated cues, whereas dopamine neurotransmission in the NAc is activated in the process of motivated exploration of cues associated with cocaine reward. Furthermore, the glutamate signaling cascade in the PFC is suggested to be a potential therapeutic target to prevent the progression of drug addiction.

Kv7 Channel Opener Retigabine Reduces Self-Administration of Cocaine but Not Sucrose in Rats

“…The reduction was greater than previously reported with flupirtine 26 , a less selective structural precursor of retigabine that activates Kv7.2/7.3 and other channels 27 . The behavioral reduction with retigabine may reflect decreased dopamine transmission, as similar doses of retigabine reportedly decreased the enhancement of striatal and cortical dopamine levels associated with noncontingent administration of cocaine 16 , which appear necessary for the acquisition of CPP 28 .…”

Immediate glucose signaling transmitted via the vagus nerve in gut-brain neural communication

“…Typically, frontal cortex neurons propagate reward-related signals via D1DR. [59][60][61][62] Though cellular level astrocytes response to dopamine via each receptor is well investigated, it is not much investigated that the detail mechanism of astrocytes to dopamine in frontal cortex under physiological condition. [63][64][65][66] To delineate the contributions of D1DR and D2DR to the activation of neurons and astrocytes under IG glucose injection, the effect of D1DR and D2DR antagonist on CaMKII-GCamp7f and Mlc-YC signals were assessed using fiber photometry (Fig.…”

Cocaine: An Updated Overview on Chemistry, Detection, Biokinetics, and Pharmacotoxicological Aspects including Abuse Pattern

“…Cocaine has been demonstrated to possess an elevated abuse potential, with experimental studies reporting it induces place preference conditioning and readily acts as reinforcer for drug self-administration [131][132][133][134]. Di Chiara and Imperato tested the effect of cocaine on extracellular dopamine content in two terminal dopaminergic brain areas of rats (the dorsal caudate nucleus and the nucleus accumbens septi), and found that the drug has the capacity to increase dopamine concentrations in both the areas, but especially in the nucleus accumbens, postulating that this ability could be a key element of drugs of abuse [135].…”