Targeted intracranial delivery of molecularly-specific therapies within intricate brain structures poses a formidable challenge due to the heterogeneity of neuronal phenotypes and functions. Here we report the use of an implantable, miniaturized neural drug delivery system permitting dynamic adjustment of pharmacotherapies. Specifically, we exploit the spatial accuracy afforded by this method...
Negative affective states can increase the rewarding value of drugs of abuse and promote drug taking. Chronic cocaine exposure increases levels of the neuropeptide dynorphin, an endogenous ligand at kappa opioid receptors (KOR) that suppresses dopamine release in the nucleus accumbens (NAc) and elicits negative affective states upon drug withdrawal. However, there is evidence that the effects...
Stress and chronic exposure to drugs of abuse can trigger addictive and depressive disorders. Both stimuli increase activity of dynorphin, a neuropeptide that acts at kappa-opioid receptors (KORs). In humans, KOR agonists cause dysphoria, raising the possibility that dynorphin modulates the depressive-like effects of stress and chronic drug use. We examined if KOR activation alters sensitivity...