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Dopamine and stress response
144A
BIOL PSYCHIATRY 1991;29:43A- 185A
Anxiety and Panic Disorders
218 THE FEAR-POTENTIATED STARTLE REFLEX AS A MEASURE OF FEAR ONSET AND OFFSET Christian Grillon, Ph.D., Rezvan Ameli, Ph.D., Michael Davis, Ph.D. Department of Psvchiato', Yale University School of Medicine, New Haven, CT 06510-3223. The startle reflex is increased by fear in both humans and animals. We have repotted that the anticipation of electric shock facilitates the startle reflex in man. In the present study, the onset and offset of fear was investigated by eliciting the startle reflex at different periods before and after the threat of electric shocks. The results indicated that during the anticipation of shocks the startle reflex gradually increased. It was maximum at the time when the administration of shock was imminent. Then, it rapidly returned to baseline. A control experiment in which subjects were asked to detect weak electric stimuli on their wrist did not produce any changes in the startle response. These results suggest that the startle reflex could be a useful tool to investigate anxiety disorders and their pharmacological treatments.
219 PLASMA CATECHOLAMINES IN PTSD: EFFECTS OF A SINGLE ORAL YOHIMBINE DOSE Mark Hamner, M.D., Bruce Diamond, Ph.D. VAMC and Medical University of South Carolina, Charleston, SC 29403 and Medical College of GA, Augusta GA 30912. Catecholamine (CA) dysregulation has been implicated in the pathophysiology of posttranmatic stress disorder (PTSD). Noradrenergic dysfunction is probably involved. We have also observed elevated plasma dopamine (DA) levels in PTSD patients. In a double-blind study, male Vietnam combat veterans with DSMIII-R PTSD (n = 10) and healthy male controls (n = 5) underwent two sessions in which they received a single 16.2 mg yohimbine or placebo. Blood samples were obtained at baseline and l and 2 hr post-drug for assay or plasma norepinephrine (NE) MHPG, DA, and HVA. The primary significant finding was elevated resting DA levels in PTSD (89.3 ~ 12 ng/ml versus 41.6 _+ 5.4 ng/ml in controls, p < 0.025). DA levels remained higher in PTSD following yohimbine challenge, but there was no significant change in either group from baseline. There were also no significant differences in MHPG, HVA, or NE in the resting or post-yohimbine conditions. The yohimbine dose may have been inadequate to elicit significant CA changes. These pilot data replicate our earlier findings suggesting a peripheral DA dysregulation in PTSD.
220 DOPAMINE AND STRESS R_ESPONSE Mark Hamner, M.D., John Entrekin, B.S., Bruce Diamond, Ph.D. VAMC and Medical University of South Carolina, Charleston, SC 29403 and Medical College of GA, Augusta GA 30912. Dopamine function is affected by acute stress; however, the role of dopamine in adaptation to acute or chronic stress is unclear. One animal model for stress-response may be the forced swim (FS) test. We hypothesized that dopaminergic drugs would alter immobility responses as a function of acute versus chronic stress. We studied male Sprague-Dawley rats (160-180 g) undergoing acute FS (AFS) or chronic FS (CFS). Animals received IP haloperidol (HAL) 0.2 mg/kg, apomorphine (APO) 0.25 mg/kg, or vehicle (CONT) 15 min prior to timing their immobility responses. They were tested on days 1,7, and 14 after the final FS. APO increased immobility in the AFS group on day 7 (APO 290 _+ 4.6 sec versus CONT 271 - 8.7 sec, p = 0.005) but not days l or 14. In the CFS group, APO increased immobility at day 14 (APO 292 +_ 4.4 sec versus CONT 278 _+ 15.5 sec, p = 0.004). HAL also increased immobility on day 14 in the CS group only (HAL 290 _ 3.3 2 sec versus CONT, p = 0.007). These data support a role for DA in stress response. The delayed effects of these DA agents on immobility and the similar effects of HAL and APO in chronic stress implicate alterations in DA receptor function.
BIOL PSYCHIATRY 1991;29:43A- 185A
Anxiety and Panic Disorders
218 THE FEAR-POTENTIATED STARTLE REFLEX AS A MEASURE OF FEAR ONSET AND OFFSET Christian Grillon, Ph.D., Rezvan Ameli, Ph.D., Michael Davis, Ph.D. Department of Psvchiato', Yale University School of Medicine, New Haven, CT 06510-3223. The startle reflex is increased by fear in both humans and animals. We have repotted that the anticipation of electric shock facilitates the startle reflex in man. In the present study, the onset and offset of fear was investigated by eliciting the startle reflex at different periods before and after the threat of electric shocks. The results indicated that during the anticipation of shocks the startle reflex gradually increased. It was maximum at the time when the administration of shock was imminent. Then, it rapidly returned to baseline. A control experiment in which subjects were asked to detect weak electric stimuli on their wrist did not produce any changes in the startle response. These results suggest that the startle reflex could be a useful tool to investigate anxiety disorders and their pharmacological treatments.
219 PLASMA CATECHOLAMINES IN PTSD: EFFECTS OF A SINGLE ORAL YOHIMBINE DOSE Mark Hamner, M.D., Bruce Diamond, Ph.D. VAMC and Medical University of South Carolina, Charleston, SC 29403 and Medical College of GA, Augusta GA 30912. Catecholamine (CA) dysregulation has been implicated in the pathophysiology of posttranmatic stress disorder (PTSD). Noradrenergic dysfunction is probably involved. We have also observed elevated plasma dopamine (DA) levels in PTSD patients. In a double-blind study, male Vietnam combat veterans with DSMIII-R PTSD (n = 10) and healthy male controls (n = 5) underwent two sessions in which they received a single 16.2 mg yohimbine or placebo. Blood samples were obtained at baseline and l and 2 hr post-drug for assay or plasma norepinephrine (NE) MHPG, DA, and HVA. The primary significant finding was elevated resting DA levels in PTSD (89.3 ~ 12 ng/ml versus 41.6 _+ 5.4 ng/ml in controls, p < 0.025). DA levels remained higher in PTSD following yohimbine challenge, but there was no significant change in either group from baseline. There were also no significant differences in MHPG, HVA, or NE in the resting or post-yohimbine conditions. The yohimbine dose may have been inadequate to elicit significant CA changes. These pilot data replicate our earlier findings suggesting a peripheral DA dysregulation in PTSD.
220 DOPAMINE AND STRESS R_ESPONSE Mark Hamner, M.D., John Entrekin, B.S., Bruce Diamond, Ph.D. VAMC and Medical University of South Carolina, Charleston, SC 29403 and Medical College of GA, Augusta GA 30912. Dopamine function is affected by acute stress; however, the role of dopamine in adaptation to acute or chronic stress is unclear. One animal model for stress-response may be the forced swim (FS) test. We hypothesized that dopaminergic drugs would alter immobility responses as a function of acute versus chronic stress. We studied male Sprague-Dawley rats (160-180 g) undergoing acute FS (AFS) or chronic FS (CFS). Animals received IP haloperidol (HAL) 0.2 mg/kg, apomorphine (APO) 0.25 mg/kg, or vehicle (CONT) 15 min prior to timing their immobility responses. They were tested on days 1,7, and 14 after the final FS. APO increased immobility in the AFS group on day 7 (APO 290 _+ 4.6 sec versus CONT 271 - 8.7 sec, p = 0.005) but not days l or 14. In the CFS group, APO increased immobility at day 14 (APO 292 +_ 4.4 sec versus CONT 278 _+ 15.5 sec, p = 0.004). HAL also increased immobility on day 14 in the CS group only (HAL 290 _ 3.3 2 sec versus CONT, p = 0.007). These data support a role for DA in stress response. The delayed effects of these DA agents on immobility and the similar effects of HAL and APO in chronic stress implicate alterations in DA receptor function.