Chronic amphetamine treatment enhances corticotropin-releasing factor-induced serotonin release in the amygdala.
Amphetamine use is associated with dysphoric states, including heightened anxiety, that emerge within 24h of withdrawal from the drug. Corticotropin-releasing factor increases serotonin release in the central nucleus of the amygdala, and this neurochemical circuitry may play a role in mediating fear and anxiety states. We have previously shown that chronic amphetamine treatment increases corticotropin-releasing factor receptor type-2 levels in the serotonergic dorsal raphe nucleus of the rat. Therefore, we hypothesized that chronic amphetamine treatment would enhance the amygdalar serotonergic response to corticotropin-releasing factor infused into the dorsal raphe nucleus. Male rats were injected once-daily with d-amphetamine (2.5mg/kg i.p., or saline) for two weeks. Serotonin release within the central nucleus of the amygdala in response to intra-raphe infusion of corticotropin-releasing factor (100 ng) was measured 24h after the last treatment in urethane-anesthetized (1.8 mg/kg, i.p.) rats using in vivo microdialysis. Rats pretreated with amphetamine showed significantly enhanced serotonin release in the central nucleus of the amygdala in response to corticotropin-releasing factor infusion when compared to saline pretreated rats. Furthermore, this enhanced response was blocked by the corticotropin-releasing factor type-2 receptor antagonist antisauvagine-30 (2 microg) infused into the dorsal raphe nucleus. These results suggest increased sensitivity to corticotropin-releasing factor as mediated by type-2 receptors following chronic amphetamine treatment, which may underlie dysphoric states observed during amphetamine withdrawal.
Scholl
Jamie L
JL
Division of Basic Biomedical Sciences and Neuroscience Group, Sanford School of Medicine, University of South Dakota, 414 E. Clark St. Vermillion, SD, USA.
Vuong
Shawn M
SM
Forster
Gina L
GL
D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000633:toxicity*; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D003913:Dextroamphetamine / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D017551:Microdialysis; D010446:Peptide Fragments / Q000494:pharmacology; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology
C101531:CRF receptor type 2; D000697:Central Nervous System Stimulants; D010446:Peptide Fragments; D018019:Receptors, Corticotropin-Releasing Hormone; C116607:antisauvagine 30; D012701:Serotonin; D003346:Corticotropin-Releasing Hormone; D003913:Dextroamphetamine