Imaging the cAMP Signaling Microdomain of the Primary Cilium Using Targeted FRET-Based Biosensors.

Optical approaches have revolutionized our view of second messenger signaling in organelles, allowing precise time-resolved assessment of soluble signaling molecules in situ. Among the most challenging of subcellular signaling microdomains to assay is the primary cilium. A petite but visually arresting organelle, the primary cilium extends from the cell surface of most non-dividing cells.

Cyclic AMP does double duty to support parallel signaling in primary cilium and cytosol.

The primary cilium maintains all of the necessary machinery to generate and interpret cAMP signals within its tiny volume, leading to the supposition that ciliary cAMP provides unique biological instructions separate from those derived from the rest of the cell body. A new paper by Truong et al. has used optogenetic and chemogenetic tricks to selectively manipulate cAMP signaling within the primary cilium.

Persistent increase of I.V. cocaine self-administration in a subgroup of C57BL/6J male mice after social defeat stress.

Rationale: Stressful life experiences can persistently increase the motivation for, and consumption of, intensely rewarding stimuli, like cocaine, over time. In rodents, intermittent versus continuous exposure to social stress engenders opposing changes to reward-related behavior, as measured by consumption of sucrose and cocaine.

Objective: The present study examines if the effects of intermittent versus continuous social stress on cocaine self-administration in mice parallel those seen in rats.

Social defeat stress and escalation of cocaine and alcohol consumption: Focus on CRF.

Both the ostensibly aversive effects of unpredictable episodes of social stress and the intensely rewarding effects of drugs of abuse activate the mesocorticolimbic dopamine systems. Significant neuroadaptations in interacting stress and reward neurocircuitry may underlie the striking connection between stress and substance use disorders. In rodent models, recurring intermittent exposure to social defeat stress appears to produce a distinct profile of neuroadaptations that translates most readily to the repercussions of social stress in humans.

Pathophysiological Bases of Comorbidity: Traumatic Brain Injury and Post-Traumatic Stress Disorder.

The high rates of traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) diagnoses encountered in recent years by the United States Veterans Affairs Healthcare System have increased public awareness and research investigation into these conditions. In this review, we analyze the neural mechanisms underlying the TBI/PTSD comorbidity. TBI and PTSD present with common neuropsychiatric symptoms including anxiety, irritability, insomnia, personality changes, and memory problems, and this overlap complicates diagnostic differentiation.

Dopamine D1 receptor agonist treatment attenuates extinction of morphine conditioned place preference while increasing dendritic complexity in the nucleus accumbens core.

The dopamine D1 receptor (D1R) has a role in opioid reward and conditioned place preference (CPP), but its role in CPP extinction is undetermined. We examined the effect of D1R agonist SKF81297 on the extinction of opioid CPP and associated dendritic morphology in the nucleus accumbens (NAc), a region involved with reward integration and its extinction. During the acquisition of morphine CPP, mice received morphine and saline on alternate days; injections were given immediately before each of eight daily conditioning sessions.

Acquisition of morphine conditioned place preference increases the dendritic complexity of nucleus accumbens core neurons.

Contexts associated with opioid reward trigger craving and relapse in opioid addiction. Effects of reward-context associative learning on nucleus accumbens (NAc) dendritic morphology were studied using morphine conditioned place preference (CPP). Morphine-conditioned mice received saline and morphine 10 mg/kg subcutaneous (s.