Date of Presentation
5-2-2024 12:00 AM
College
Rowan-Virtua School of Osteopathic Medicine
Poster Abstract
Cocaine Use Disorder persists as a significant public health concern in the United States. Recent epidemiological data indicate that rates of cocaine-involved overdose deaths are rising, and treatment of Cocaine Use Disorder is challenging due to a lack of FDA-approved medications to help patients achieve abstinence and avoid relapse. Stress can precipitate cocaine craving and trigger relapse episodes, however the underlying neural circuitry by which stressors drive cocaine seeking is not completely understood. Our laboratory has recently identified the potential involvement of the rostrolateral aspect of the periaqueductal gray (rlPAG) in psychosocial stress-induced cocaine-seeking behavior using a rodent model of cocaine relapse. Neuroanatomical evidence points to a dense monosynaptic input from the lateral hypothalamus (LH) to the rlPAG, yet whether activity within the LH is also associated specifically with psychosocial-stress induced cocaine seeking has not been previously explored. In this study, adult male and female Long-Evans rats were allowed to self-administer cocaine (0.5 mg/kg/inf, IV) in 2-h daily sessions for 20 sessions. During sessions 11, 14, 17, and 20, a tactile cue (perforated polycarbonate enclosure) was placed within the operant chamber, and these sessions were immediately followed by either social defeat stress (SDS, n=16; 8M, 8F) or a no-stress empty-cage control condition (EC, n=12; 6M, 6F). Beginning on day 21, animals underwent extinction training during which lever-presses were not reinforced. Once responding was extinguished, rats were re-exposed to the tactile cue that signaled their assigned stress/no-stress stimulus, and reinstatement of cocaine-seeking was measured for 2 h under extinction conditions. Immediately after the reinstatement test, animals were sacrificed, and brains collected and processed via immunohistochemistry for expression of the immediate early gene c-Fos and the neuropeptide orexin within the LH and neighboring Perifornical Area (PfA). Despite no significant difference between groups in the number of Fos+ or orexin+ cells in the LH/PfA, there was a significant positive correlation between Fos expression in non-orexinergic LH/PfA cells and stress-induced cocaine-seeking magnitude specifically within males. Additionally, Fos expression in these cells was also significantly and positively correlated with Fos expression in the rostrolateral periaqueductal gray. Collectively, these findings suggest that a LH --> rlPAG projection may be selectively engaged during psychosocial stress-induced cocaine seeking behavior in male rats.
Keywords
Cocaine Use Disorder, Cocaine-Related Disorders, Fos expression, fos Genes, Gene Expression, Lateral hypothalamus, Rats
Disciplines
Disease Modeling | Genetic Processes | Medical Cell Biology | Medical Neurobiology | Medicine and Health Sciences | Nervous System | Substance Abuse and Addiction
Document Type
Poster
Included in
Disease Modeling Commons, Genetic Processes Commons, Medical Cell Biology Commons, Medical Neurobiology Commons, Nervous System Commons, Substance Abuse and Addiction Commons
Fos Expression in Lateral Hypothalamus/Perifornical Area is Correlated with Psychosocial Stress-Induced Cocaine-Seeking Behavior in a Sex-Specific Manner
Cocaine Use Disorder persists as a significant public health concern in the United States. Recent epidemiological data indicate that rates of cocaine-involved overdose deaths are rising, and treatment of Cocaine Use Disorder is challenging due to a lack of FDA-approved medications to help patients achieve abstinence and avoid relapse. Stress can precipitate cocaine craving and trigger relapse episodes, however the underlying neural circuitry by which stressors drive cocaine seeking is not completely understood. Our laboratory has recently identified the potential involvement of the rostrolateral aspect of the periaqueductal gray (rlPAG) in psychosocial stress-induced cocaine-seeking behavior using a rodent model of cocaine relapse. Neuroanatomical evidence points to a dense monosynaptic input from the lateral hypothalamus (LH) to the rlPAG, yet whether activity within the LH is also associated specifically with psychosocial-stress induced cocaine seeking has not been previously explored. In this study, adult male and female Long-Evans rats were allowed to self-administer cocaine (0.5 mg/kg/inf, IV) in 2-h daily sessions for 20 sessions. During sessions 11, 14, 17, and 20, a tactile cue (perforated polycarbonate enclosure) was placed within the operant chamber, and these sessions were immediately followed by either social defeat stress (SDS, n=16; 8M, 8F) or a no-stress empty-cage control condition (EC, n=12; 6M, 6F). Beginning on day 21, animals underwent extinction training during which lever-presses were not reinforced. Once responding was extinguished, rats were re-exposed to the tactile cue that signaled their assigned stress/no-stress stimulus, and reinstatement of cocaine-seeking was measured for 2 h under extinction conditions. Immediately after the reinstatement test, animals were sacrificed, and brains collected and processed via immunohistochemistry for expression of the immediate early gene c-Fos and the neuropeptide orexin within the LH and neighboring Perifornical Area (PfA). Despite no significant difference between groups in the number of Fos+ or orexin+ cells in the LH/PfA, there was a significant positive correlation between Fos expression in non-orexinergic LH/PfA cells and stress-induced cocaine-seeking magnitude specifically within males. Additionally, Fos expression in these cells was also significantly and positively correlated with Fos expression in the rostrolateral periaqueductal gray. Collectively, these findings suggest that a LH --> rlPAG projection may be selectively engaged during psychosocial stress-induced cocaine seeking behavior in male rats.