Biology subjects

Kelley, L. K.

Publications and source records attributed to Kelley, L. K..

3 recordsLinked to original sources

bioRxiv2021

Chronic THC vapor rescues inflammation-related thermal hyperalgesia and causes cell type-specific modifications in vlPAG neurons

AbstractIn an effort to reduce reliance on opioids for the treatment of pain in the clinic, ongoing work is testing the utility of cannabinoid drugs as a potential alternative for treatment of chronic pain. We tested chronic THC vapor inhalation effects on thermal nociception and mechanical sensitivity, as well as midbrain (i.e., ventrolateral periaqueductal gray [vlPAG]) neuronal function, in adult male and female Wistar rats with chronic inflammatory pain (CFA treatment). We report that chronic THC vapor inhalation rescues both thermal hyperalgesia and mechanical hypersensitivity in males treated with CFA, but only thermal hyperalgesia in CFA females. Most of the anti-hyperalgesic effects of chronic THC vapor were still observable 24 hours after cessation of the last THC exposure. We also report that chronic THC vapor inhalation modulates intrinsic and synaptic properties of vlPAG neurons, including reductions in action potential firing rate and spontaneous inhibitory synaptic transmission in males, and that these effects occur specifically in neurons that respond to current input with a "delayed" firing phenotype. Treatment with CFA led to increased firing rate and increased sIPSC amplitude in vlPAG neurons of female rats, and chronic THC vapor rescued sIPSC amplitudes to control levels - these effects were specific to vlPAG neurons categorized as having an "onset" firing phenotype. Ongoing work is exploring sex-specific mechanisms (e.g., CB1 receptor) of THC vapor rescue effects in the vlPAG of rats treated with CFA, and further exploring the vlPAG cell types impacted by CFA treatment and chronic THC vapor inhalation. Significance StatementMany adults in the U.S. with pain self-medicate with THC and cannabis, and many humans use e-cigarette type devices filled with cannabis extracts to self-administer THC and other constituents of the marijuana plant. Until recently, most rodent studies of THC effects on brain and behavior have used injection procedures and male rats. Here, we tested the effect of chronic THC vapor inhalation on pain-related behaviors and midbrain neural circuit function in adult male and female Wistar rats. As predicted, chronic THC vapor inhalation rescued chronic inflammatory pain effects on behavior and midbrain neuronal function.

neuroscience↗

bioRxiv2020

Alcohol dependence activates ventral tegmental area projections to central amygdala in male mice and rats

The neural adaptations that occur during the transition to alcohol dependence are not entirely understood, but may include a gradual recruitment of brain stress circuitry by mesolimbic reward circuitry that is activated during early stages of alcohol use. Here, we focused on dopaminergic and non-dopaminergic projections from the ventral tegmental area (VTA), important for mediating acute alcohol reinforcement, to the central nucleus of the amygdala (CeA), important for alcohol dependence-related negative affect and escalated alcohol drinking. The VTA projects directly to the CeA, but the functional relevance of this circuit is not fully established. Therefore, we combined retrograde and anterograde tracing, anatomical, and electrophysiological experiments in mice and rats to demonstrate that the CeA receives input from both dopaminergic and non-dopaminergic projection neurons primarily from the lateral VTA. We then used slice electrophysiology and fos immunohistochemistry to test the effects of alcohol dependence on activity and activation profiles of CeA-projecting neurons in the VTA. Our data indicate that alcohol dependence activates midbrain projections to the central amygdala, suggesting that VTA projections may trigger plasticity in the CeA during the transition to alcohol dependence and that this circuit may be involved in mediating behavioral dysregulation associated with alcohol dependence.

neuroscience↗

bioRxiv2019

Nicotine e-cigarette vapor inhalation effects on nicotine & cotinine plasma levels and somatic withdrawal signs in adult male Wistar rats

RationaleNon-contingent chronic nicotine exposure procedures have evolved rapidly in recent years, culminating in Electronic Nicotine Delivery Systems (ENDS or e-cigarettes) to deliver vaporized drugs to rodents in standard housing chambers.\n\nObjectivesThe aim of the current work was to use ENDS to test concentration-dependent effects of nicotine e-cigarette vapor inhalation on blood-nicotine concentrations, blood-cotinine concentrations, and somatic withdrawal signs over time in rats.\n\nMethodsMale Wistar rats were exposed to vapor containing various concentrations of nicotine (20, 40, 80 mg/mL) for 11 days through ENDS, and blood concentrations of nicotine and cotinine, the major proximate metabolite of nicotine, as well as spontaneous and precipitated somatic withdrawal signs were measured over time (across days of exposure and over hours after termination of vapor exposure).\n\nResultsExposing male Wistar rats to non-contingent nicotine vapor inhalation through ENDS produces somatic withdrawal symptoms and measurable blood-nicotine and blood-cotinine levels that change according to 1) concentration of nicotine in vape solution, 2) number of days of nicotine vapor exposure, 3) time since termination of nicotine vapor exposure, and 4) relative to the withdrawal signs, whether withdrawal was spontaneous or precipitated (by mecamylamine).\n\nConclusionsThe data presented here provide parameters that can be used as a reasonable starting point for future work that employs ENDS to deliver non-contingent nicotine vapor in rats, although many parameters can and should be altered to match the specific goals of future work.

neuroscience↗