Chronic alcohol remodels prefrontal neurons and disrupts NMDAR-mediated fear extinction encoding.

Alcoholism is frequently co-morbid with post-traumatic stress disorder, but it is unclear how alcohol affects the neural circuits mediating recovery from trauma. We found that chronic intermittent ethanol (CIE) impaired fear extinction and remodeled the dendritic arbor of medial prefrontal cortical (mPFC) neurons in mice. CIE impaired extinction encoding by infralimbic mPFC neurons in vivo and functionally downregulated burst-mediating NMDA GluN1 receptors.

Probing the modulation of acute ethanol intoxication by pharmacological manipulation of the NMDAR glycine co-agonist site.

Background: Stimulating the glycine(B) binding site on the N-methyl-d-aspartate ionotropic glutamate receptor (NMDAR) has been proposed as a novel mechanism for modulating behavioral effects of ethanol (EtOH) that are mediated via the NMDAR, including acute intoxication. Here, we pharmacologically interrogated this hypothesis in mice.

Methods: Effects of systemic injection of the glycine(B) agonist, d-serine, the GlyT-1 glycine transporter inhibitor, ALX-5407, and the glycine(B) antagonist, L-701,324, were tested for the effects on EtOH-induced ataxia, hypothermia, and loss of righting reflex (LORR) duration in C57BL/6J (B6) and 129S1/SvImJ (S1) inbred mice.

Genetic strain differences in learned fear inhibition associated with variation in neuroendocrine, autonomic, and amygdala dendritic phenotypes.

Mood and anxiety disorders develop in some but not all individuals following exposure to stress and psychological trauma. However, the factors underlying individual differences in risk and resilience for these disorders, including genetic variation, remain to be determined. Isogenic inbred mouse strains provide a valuable approach to elucidating these factors.

Effects of chlordiazepoxide on predator odor-induced reductions of playfulness in juvenile rats.

The extent to which a non-sedative dose of chlordiazepoxide (CDP) is able to modify the behavioral responses toward a predator odor was assessed in juvenile rats. Play behavior was suppressed and defensive behaviors were enhanced in the presence of a collar previously worn by a cat, when tested 24 h later in the same context as that where the exposure occurred, and when tested in a context different than that in which the exposure occurred for up to 3 h after exposure. CDP had no effect on the ability of cat odor to suppress play when rats were tested in the presence of the odor or when tested 24 h later in the same context where that exposure occurred.