Hypothalamic-pituitary-adrenal axis activity in post-traumatic stress disorder and cocaine use disorder

Abstract

Post-traumatic stress disorder (PTSD) is often comorbid with cocaine use disorder (CUD), but little is known about hypothalamic-pituitary-adrenal (HPA) axis function in PTSD + CUD. Here we review the clinical and pre-clinical literature of PTSD and CUD with the goal of generating hypotheses about HPA axis activity in comorbid PTSD + CUD. Low glucocorticoid (CORT) levels immediately after trauma exposure are associated with PTSD. CORT administered within 12 h of trauma exposure reduces later PTSD symptoms. Weeks-years after trauma, meta-analyses find lower CORT levels in patients with PTSD relative to never-traumatized controls; the same is found in a pre-clinical model of PTSD. In rodents, reduced basal CORT levels are consistently found after chronic cocaine self-administration. Conversely, increased CORT levels are found in CUD patients during the first 2 weeks of cocaine abstinence. There is evidence for CORT hyper-suppression after dexamethasone, high glucocorticoid receptor (GR) number pre-trauma, and increased GR translocation to the nucleus in PTSD. Hyper-suppression of HPA axis activity after dexamethasone suggests that PTSD individuals may have increased anterior pituitary GR. Given evidence for decreased anterior pituitary GR in rats that self-administer cocaine, PTSD + CUD individuals may have normal GR density and low basal CORT levels during late abstinence. Future studies should aim to reconcile the differences in pre-clinical and clinical basal CORT levels during cocaine and assess HPA axis function in both rodent models of CUD that consider stress-susceptibility and in PTSD + CUD individuals. Although additional studies are necessary, individuals with PTSD + CUD may benefit from behavioral and psychopharmacological treatments to normalize HPA axis activity.

LAY SUMMARY

• Post-traumatic stress disorder (PTSD) is often comorbid with cocaine use disorder (CUD), but little is known about the hypothalamic-pituitary-adrenal (HPA) axis function in PTSD + CUD. The current review provides a synthesis of available clinical and pre-clinical data on PTSD and CUD with the goal of generating hypotheses about HPA axis activity in comorbid PTSD + CUD. While this review finds ample evidence supporting aberrant HPA axis activity in both PTSD and CUD, it suggests that more research is needed to understand the unique changes HPA axis activity in PTSD + CUD, as well as the bidirectional relationship between stress-susceptibility and motivation to seek cocaine.

Keywords:

• Cortisol
• corticosterone
• reinstatement
• relapse
• GR
• dexamethasone

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by a pilot grant from the Center for OCD, Anxiety, and Related Disorders (COARD) at University of Florida.

Notes on contributors

Natalie A. Hadad

Natalie Aviva Hadad earned a M.A. in Developmental Psychology with Summa Cum Laude Honors from Teachers College Columbia University. She earned her Ph.D. in Psychology from the University of Florida in August 2016. She is currently an Assistant Professor of Psychology at Santa Fe College in Gainesville, FL.

Marek Schwendt

Marek Schwendt earned his Ph.D. from P.J. Safarik University, Slovakia, followed by post-doctoral training in neuroscience at the Medical University of South Carolina. He is currently an Assistant Professor of Psychology at the University of Florida, where his research focuses on the neurobiology of cognitive, emotional, and motivational deficits produced by stress and drugs of abuse using animal models.

Lori A. Knackstedt

Lori A. Knackstedt earned her Ph.D. in Psychology at the University of California, Santa Barbara. She next conducted a post-doctoral fellowship in the Neuroscience Department of the Medical University of South Carolina. She is now an Associate Professor of Psychology at the University of Florida. Her work focuses on long term adaptations to the glutamate and dopamine neurotransmitter systems in response to stress and/or substance use.