Kappa-opioid receptor antagonism in the nucleus accumbens shell distinguishes escalated alcohol consumption and negative affective-like behavior from physiological withdrawal in alcohol-dependence.

Alcohol use disorder (AUD) is a chronic relapsing disease that is deleterious at individual, familial, and societal levels. Although AUD is one of the highest preventable causes of death in the USA, therapies for the treatment of AUD are not sufficient given the heterogeneity of the disorder and the limited number of approved medications. To provide better pharmacological strategies, it is important to understand the neurological underpinnings of AUD.

Recapitulating phenotypes of alcohol dependence via overexpression of Oprk1 in the ventral tegmental area of non-dependent TH::Cre rats.

The dynorphin (DYN)/kappa-opioid receptor (KOR) system is involved in dysphoria and negative emotional states. Dysregulation of KOR function promotes maladaptive behavioral regulation during withdrawal associated with alcohol dependence. Mesolimbic dopaminergic (DA) projections from the ventral tegmental area (VTA) innervate the extended amygdala circuitry and presynaptic KORs attenuate DA in these regions leading to an excessive alcohol consumption and negative affective-like behavior, whereas mesocortical KOR-regulated DA projections have been implicated in executive function and decision-making.

Input of hair field afferents to a descending interneuron.

In insects the tactile sense is important for near-range orientation and is involved in various behaviors. Nocturnal insects, such as the stick insect , continuously explore their surroundings by actively moving their antennae when walking. Upon antennal contact with objects, stick insects show a targeted front-leg movement.

Bimodal modulation of background activity in an identified descending interneuron.

In the absence of any obvious input, sensory neurons and interneurons can display resting or spontaneous activity. This is often regarded as noise and removed through trial averaging, although it may reflect history-dependent modulation of tuning or fidelity and, thus, be of functional relevance to downstream interneurons. We investigated the history dependence of spontaneous activity in a pair of identified, bimodal descending interneurons of the stick insect, called contralateral ON-type velocity-sensitive interneurons (cONv).