Chronic amphetamine treatment enhances corticotropin-releasing factor-induced serotonin release in the amygdala

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Abstract

Amphetamine use is associated with dysphoric states, including heightened anxiety, that emerge within 24. h 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 (2.5. mg/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 24. h 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 (2μg) 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.

Original languageEnglish (US)
Pages (from-to)80-87
Number of pages8
JournalEuropean Journal of Pharmacology
Volume644
Issue number1-3
DOIs
StatePublished - Oct 1 2010

Keywords

  • (Rat)
  • CRF receptor
  • Central nucleus of the amygdala
  • Dorsal raphe nucleus
  • Microdialysis

ASJC Scopus subject areas

  • Pharmacology

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