Acute, but not repeated, cocaine exposure alters allopregnanolone levels in the midbrain of male and female rats.

RATIONALE: Multiple psychiatric disorders are associated with altered brain and serum levels of neuroactive steroids, including the endogenous GABAergic steroid, allopregnanolone. Clinically, chronic cocaine use was correlated with decreased levels of pregnenolone. Preclinically, the effect of acute cocaine on allopregnanolone levels in rodents has had mixed results, showing an increase or no change in allopregnanolone levels in some brain regions. OBJECTIVE: We hypothesized that cocaine acutely increases allopregnanolone levels, but repeated cocaine exposure decreases allopregnanolone levels compared to controls. METHODS: We performed two separate studies to determine how systemic administration of 15 mg/kg cocaine (1) acutely or (2) chronically alters brain (olfactory bulb, frontal cortex, dorsal striatum, and midbrain) and serum allopregnanolone levels in adult male and female Sprague-Dawley rats. RESULTS: Cocaine acutely increased allopregnanolone levels in the midbrain, but not in olfactory bulb, frontal cortex, or dorsal striatum. Repeated cocaine did not persistently (24 h later) alter allopregnanolone levels in any region in either sex. However, allopregnanolone levels varied by sex across brain regions. In the acute study, we found that females had significantly higher allopregnanolone levels in serum and olfactory bulb relative to males. In the repeated cocaine study, females had significantly higher allopregnanolone levels in olfactory bulb, frontal cortex, and serum. Finally, acute cocaine increased allopregnanolone levels in the frontal cortex of females in proestrus, relative to non-proestrus stages. CONCLUSION: Collectively these results suggest that allopregnanolone levels vary across brain regions and by sex, which may play a part in differential responses to cocaine by sex.

Intracortical Microelectrode Array Unit Yield under Chronic Conditions: A Comparative Evaluation.

While microelectrode arrays (MEAs) offer the promise of elucidating functional neural circuitry and serve as the basis for a cortical neuroprosthesis, the challenge of designing and demonstrating chronically reliable technology remains. Numerous studies report "chronic" data but the actual time spans and performance measures corresponding to the experimental work vary. In this study, we reviewed the experimental durations that constitute chronic studies across a range of MEA types and animal species to gain an understanding of the widespread variability in reported study duration. For rodents, which are the most commonly used animal model in chronic studies, we examined active electrode yield (AEY) for different array types as a means to contextualize the study duration variance, as well as investigate and interpret the performance of custom devices in comparison to conventional MEAs. We observed wide-spread variance within species for the chronic implantation period and an AEY that decayed linearly in rodent models that implanted commercially-available devices. These observations provide a benchmark for comparing the performance of new technologies and highlight the need for consistency in chronic MEA studies. Additionally, to fully derive performance under chronic conditions, the duration of abiotic failure modes, biological processes induced by indwelling probes, and intended application of the device are key determinants.

Chronic Intracortical Recording and Electrochemical Stability of Thiol-ene/Acrylate Shape Memory Polymer Electrode Arrays.

Current intracortical probe technology is limited in clinical implementation due to the short functional lifetime of implanted devices. Devices often fail several months to years post-implantation, likely due to the chronic immune response characterized by glial scarring and neuronal dieback. It has been demonstrated that this neuroinflammatory response is influenced by the mechanical mismatch between stiff devices and the soft brain tissue, spurring interest in the use of softer polymer materials for probe encapsulation. Here, we demonstrate stable recordings and electrochemical properties obtained from fully encapsulated shape memory polymer (SMP) intracortical electrodes implanted in the rat motor cortex for 13 weeks. SMPs are a class of material that exhibit modulus changes when exposed to specific conditions. The formulation used in these devices softens by an order of magnitude after implantation compared to its dry, room-temperature modulus of ~2 GPa.