Association between intravenous ketamine-induced stress hormone levels and long-term fear memory renewal in Sprague-Dawley rats

• Published in: Behavioural brain research Vol. 378; p. 112259
• Main Authors: Radford, Kennett D., Spencer, Haley F., Zhang, Michael, Berman, Rina Y., Girasek, Quinn L., Choi, Kwang H.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 27-01-2020
• Subjects: Administration, Intravenous; Anesthetics, Dissociative - administration & dosage; Anesthetics, Dissociative - pharmacology; Animals; Antinociception; Behavior, Animal - drug effects; Corticosterone; Corticosterone - blood; Disease Models, Animal; Extinction, Psychological - drug effects; Fear - drug effects; Fear memory; Ketamine; Ketamine - administration & dosage; Ketamine - pharmacology; Male; Memory, Long-Term - drug effects; Mental Recall - drug effects; Nociception - drug effects; Progesterone; Progesterone - blood; PTSD; Rats; Rats, Sprague-Dawley; Stress, Psychological - drug therapy; Stress, Psychological - metabolism; PTSD; Fear memory; Antinociception; Ketamine; Progesterone; Corticosterone
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2019.112259

•An IV ketamine infusion (10 mg/kg) produces sedation, antinociception, and elevation of corticosterone and progesterone levels in rats.•Post-fear conditioning IV ketamine infusion does not alter long-term fear memory in rats.•However, animals with greater stress hormone release after ketamine infusion exhibit greater long-term fear memory renewal.•Individual differences in sensitivity to acute ketamine may predict the vulnerability to develop long-term fear-related disorders.
Ketamine is a multimodal dissociative anesthetic and analgesic that is widely used after traumatic injury. We previously reported that an analgesic dose of intravenous (IV) ketamine infusion (10 mg/kg, 2-h) after fear conditioning enhanced short-term fear memory in rats. Here, we investigated the effects of the same dose of an IV ketamine infusion on plasma stress hormone levels and long-term fear memory in rats. Adult male Sprague-Dawley rats (9-week-old with an average weight of 308 g upon arrival) received a ketamine infusion (0 or 10 mg/kg, 2-h) immediately after auditory fear conditioning (three auditory tone and footshock [0.6 mA, 1-s] pairings) on Day 0. After the infusion, a blood sample was collected from a jugular vein catheter for corticosterone and progesterone assays, and each animal was tested on tail flick to measure thermal antinociception. One week later, animals were tested on fear extinction acquisition (Day 7), fear extinction retrieval (Day 8), and fear renewal (Day 9). The IV ketamine infusion, compared to the saline infusion, reduced locomotor activity (sedation), increased tail flick latency (antinociception), and elevated plasma corticosterone and progesterone levels. The ketamine infusion did not alter long-term fear memory extinction or fear renewal. However, elevated corticosterone and progesterone levels resulting from the ketamine infusion were correlated with sedation, antinociception, and long-term fear memory renewal. These results suggest that individual differences in sensitivity to acute ketamine may predict vulnerability to develop fear-related disorders.