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HIV Transgenic Rats Demonstrate Impaired Sensorimotor Gating But Are Insensitive to Cannabinoid (Δ9-Tetrahydrocannabinol)-Induced Deficits

Roberts BZ, Minassian A, Halberstadt AL, He YV, Chatha M, Geyer MA, Grant I, Young JW

Background: HIV-associated neurocognitive disorder (HAND) is commonly observed in persons living with HIV (PWH) and is characterized by cognitive deficits implicating disruptions of fronto-striatal neurocircuitry. Such circuitry is also susceptible to alteration by cannabis and other drugs of abuse. PWH use cannabis at much higher rates than the general population, thus prioritizing the characterization of any interactions between HIV and cannabinoids on cognitively relevant systems. Prepulse inhibition (PPI) of the startle response, the process by which the motor response to a startling stimulus is attenuated by perception of a preceding non-startling stimulus, is an operational assay of fronto-striatal circuit integrity that is translatable across species. PPI is reduced in PWH. The HIV transgenic (HIVtg) rat model of HIV infection mimics numerous aspects of HAND, although to date the PPI deficit observed in PWH has yet to be fully recreated in animals.

Electrophysiological biomarkers of behavioral dimensions from cross-species paradigms

Cavanagh JF, Gregg D, Light GA, Olguin SL, Sharp RF, Bismark AW, Bhakta SG, Swerdlow NR, Brigman JL, Young JW

There has been a fundamental failure to translate preclinically supported research into clinically efficacious treatments for psychiatric disorders. One of the greatest impediments toward improving this species gap has been the difficulty of identifying translatable neurophysiological signals that are related to specific behavioral constructs.

Chronic antipsychotic treatment exerts limited effects on the mania-like behavior of dopamine transporter knockdown mice

Cope ZA & Kenton JA, Minassian A, Martin MV, Perry W, Bundgaard C, Arnt J, van Enkhuizen J, Geyer MA, Young JW

Background: Bipolar disorder is a life-threatening disorder linked to dopamine transporter (DAT) polymorphisms, with reduced DAT levels seen in positron emission tomography and postmortem brains.

Convergent observations of MK-801-induced impairment in rat 5C-CPT performance across laboratories: reversal with a D 1 but not nicotinic agonist

Grottick AJ, MacQueen DL, Barnes SA, Carroll C, Sanabria EK, Bobba V, Young JW

Cognitive function is closely linked to functional outcomes in psychiatric disorders such as schizophrenia, however developing effective treatments for cognitive dysfunction have proven elusive. Potential reasons for this may include the complexity of diseases, the absence of appropriate and translatable animal tests of cognitive dysfunction, and the reproducibility of findings. Attention is a key component of cognitive function traditionally assessed in the clinic using a variant of the continuous performance test (CPT).

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