Document Type
Article
Version Deposited
Submitted for publication (PrePrint)
Publication Date
1-22-2025
Publication Title
bioRxiv
DOI
10.1101/2025.01.22.634146
Abstract
Psychosocial stressors are known to promote cocaine craving and relapse in humans but are infrequently employed in preclinical relapse models. Consequently, the underlying neural circuitry by which these stressors drive cocaine seeking has not been thoroughly explored. Using Fos expression analyses, we sought to examine whether the ventromedial hypothalamus (VMH) or periaqueductal gray (PAG), two critical components of the brain's hypothalamic defense system, are activated during psychosocial stress-induced cocaine seeking. Adult male and female rats self-administered cocaine (0.5 mg/kg/inf IV, fixed-ratio 1 schedule, 2 h/session) over 20 sessions. On sessions 11, 14, 17, and 20, a tactile cue was present in the operant chamber that signaled impending social defeat stress (n=16, 8/sex), footshock stress (n=12, 6/sex), or a no-stress control condition (n=12, 6/sex) immediately after the session's conclusion. Responding was subsequently extinguished, and rats were tested for reinstatement of cocaine seeking during re-exposure to the tactile cue that signaled their impending stress/no-stress post-session event. All experimental groups displayed significant reinstatement of cocaine seeking, but Fos analyses indicated that neural activity within the rostrolateral PAG (rPAGl) was selectively correlated with cocaine-seeking magnitude in the socially-defeated rats. rPAGl activation was also associated with active-defense coping behaviors during social defeat encounters and with Fos expression in prelimbic prefrontal cortex and orexin-negative cells of the lateral hypothalamus/perifornical area in males, but not females. These findings suggest a potentially novel role for the rPAGl in psychosocial stress-induced cocaine seeking, perhaps in a sex-dependent manner.
Recommended Citation
Hinds, Nicole M; Wojtas, Ireneusz D; Pulley, Desta M; McDonald, Stephany J; Spencer, Colton D; Sudarikov, Milena; Hubbard, Nicole E; Kulick-Soper, Colin M; de Guzman, Samantha; Hayden, Sara; Debski, Jessica J; Patel, Bianca; Fox, Douglas P; and Manvich, Daniel F, "Fos Expression in the Periaqueductal Gray, But Not the Ventromedial Hypothalamus, Is Correlated With Psychosocial Stress-Induced Cocaine-Seeking Behavior in Rats" (2025). Rowan-Virtua School of Osteopathic Medicine Departmental Research. 270.
https://rdw.rowan.edu/som_facpub/270
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Published Citation
Hinds NM, Wojtas ID, Pulley DM, McDonald SJ, Spencer CD, Sudarikov M, Hubbard NE, Kulick-Soper CM, de Guzman S, Hayden S, Debski JJ, Patel B, Fox DP, Manvich DF. Fos expression in the periaqueductal gray, but not the ventromedial hypothalamus, is correlated with psychosocial stress-induced cocaine-seeking behavior in rats. bioRxiv [Preprint]. 2025 Jan 22:2025.01.22.634146. doi: 10.1101/2025.01.22.634146. PMID: 39896664; PMCID: PMC11785129.
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Comments
This is a preprint.
It has not yet been peer reviewed by a journal. The National Library of Medicine is running a pilot to include preprints that result from research funded by NIH in PMC and PubMed.