Possible Interaction: Cocaine and Leptin

“ Leptin activates tyrosine kinase, Janus kinase 2, and signal transducer and activator of transcription 3, leading to increased levels of anorexigenic peptides, e.g., α‐melanocyte stimulating hormone and cocaine‐ and amphetamine‐regulated transcript, and inhibition of orexigenic peptides, e.g., neuropeptide Y and agouti‐related peptide.”

“ Leptin activates neurons containing alpha-melanocyte stimulating hormone and cocaine- and amphetamine-regulated transcript peptides, resulting in increases in sympathetic activity and blood pressure.”

“The effects of leptin may also be modulated by factors such as the corticotrophin-releasing factor (CRF), cocaine and amphetamine-regulated transcript (CART), orexins and galanin.”

“Interestingly, leptin in the NAcc core significantly blocks the increase of GluA1 phosphorylation levels at serine 845 induced by acute administration of cocaine.”

“ Leptin in the rat’s nucleus accumbens (NAcc) … the effects of acute administration of cocaine on both locomotor activity and the phosphorylation levels of glycogen synthase kinase 3&bgr;. In the present … levels of GluA1 after bilateral microinjections of leptin in this site followed by acute administration of cocaine.”

“Interestingly, leptin in the NAcc core significantly disrupts acute cocaine ’s effects on both locomotor activity and signaling molecules.”

“These results indicate that leptin in the NAcc core has a negative regulatory role in acute cocaine’ effects, and suggest that GSK3&bgr; may play a major role in mediating these processes.”

“However, the role of leptin signaling in regulating the response to cocaine remains unclear.”

“First, we report that cocaine and the expectancy of cocaine each depresses plasma leptin levels.”

“Here we report reciprocal inhibition between the reward-related effects of leptin and the reward-related effects of cocaine in rats.”

“Second, we … exogenous leptin , given systemically or directly into the … tegmental area, attenuates the ability of cocaine to elevate dopamine levels in the nucleus accumbens, the ability of cocaine to establish a conditioned … preference, and the ability of cocaine-predictive stimuli to prolong responding in extinction of cocaine-seeking.”

“Thus, whereas leptin represents an endogenous antagonist of the habit-forming and habit-sustaining effects of cocaine , this antagonism is attenuated by cocaine and comes to be attenuated by the expectancy of cocaine.”

“As anticipated, the intracerebroventricular infusion of leptin reduced fasting-induced elevations in NPY and AGRP mRNA and increased proopiomelanocortin and cocaine and amphetamine-regulated transcript mRNA in the arcuate nucleus.”

“ Leptin may act as a negative feedback signal to the hypothalamic control of appetite through suppression of neuropeptide Y (NPY) secretion and stimulation of cocaine and amphetamine regulated transcript (CART).”