Corticotropin‐Releasing Factor Stimulates Catecholamine Release in Hypothalamus and Prefrontal Cortex in Freely Moving Rats as Assessed by Microdialysis

Abstract

Abstract:In vivo microdialysis was used to measure changes in extracellular concentrations of catecholamines and indoleamines in freely moving rats in response to administration of corticotropin-releasing factor (CRF). Dialysis probes were placed stereotaxically in either the medial hypothalamus or the medial prefrontal cortex. We used a repeated-measures design in which each rat received artificial CSF or one dose of C R F 3-4 h apart, and each subject was retested with the same treatments in the reverse order 5-7 days later. With the dialysis probe in the hypothalamus, intracerebroventricular administration of C R F (17 or 330 pmol) dose-dependently increased dialysate concentrations of norepinephrine (NE), dopamine (DA), and all their measurable catabolites except normetanephrine. The effects on NE were substantially greater than those on DA. Dialysate concentrations of serotonin could not be measured reliably, but those of its catabolite, 5-hydroxyindoleacetic acid, were also elevated. Concentrations of NE and DA were elevated within the first one or two (20 min) collection periods, with a peak response at -1-2 h. Dialysate concentrations of catecholamines and metabolites normally returned to baseline within 3 h. Similar data were obtained with dialysis probes in the medial prefrontal cortex after intracerebroventricular administration of 17 or 167 pmol of CRF, except that the increases in DA exceeded those of NE in this region. lntraperitoneal administration ofCRF (1 nmol) similarly elevated dialysate concentrations of NE, DA, 5-hydroxyindoleacetic acid, and all catecholamine catabolites except normetanephrine in both medial hypothalamus and medial prefrontal cortex. These results support earlier neurochemical data suggesting that C R F administered both centrally and peripherally stimulates the release of both DA and NE in the brain.

Elevated Concentrations of CRF in the Locus Coeruleus of Depressed Subjects

“…Intracerebroventricular administration of CRF increases release of NE as measured by microdialysis probes sited in the medial hypothalamus (Lavicky and Dunn, 1993). This stimulatory effect of NE on CRF release has been observed in rat hypothalamic explants and was blocked by beta-adrenergic receptor antagonists, but not alpha adrenergic receptor blocking drugs (Tsagarakis et al, 1988).…”

Blockade of mesolimbic dopamine D3 receptors inhibits stress-induced reinstatement of cocaine-seeking in rats

“…Stress also reliably reinstates drug-seeking in animals after extinction of heroin-taking, cocaine-taking, nicotine-taking, or alcohol-taking behavior (Shaham et al 2000a). Although noradrenergic and CRF neurotransmitter mechanisms appear to underlie stress-triggered reinstatement (Lavicky and Dunn 1993;Shaham et al 1997;Shaham et al 2000a;Leri et al 2002 for review), a role for DA has not been ruled out. The present study demonstrates that selective D 3 receptor antagonism blocks stress-induced reinstatement of cocaine-seeking behavior, supporting the involvement of DA and D 3 receptors in stress-induced reinstatement.…”

“…Stress may also activate mesolimbic DA by releasing corticotrophinreleasing factor (CRF) in midbrain and amygdala (Lavicky and Dunn 1993;Shaham et al 1997). Moreover, such stress-induced elevation of NAcc DA correlates temporally with reinstatement of heroin-seeking (Shaham and Stewart 1995), which can be blocked by the mixed DA antagonist flupenthixol, but not by the D 1 antagonist SCH-23390 or the D 2 antagonist raclopride (Shaham and Stewart 1996).…”

Increase of extracellular corticotropin-releasing factor-like immunoreactivity levels in the amygdala of awake rats during restraint stress and ethanol withdrawal as measured by microdialysis

“…A recent microdialysis experiment (Tanaka et al, 1991) showed that the temporal profile of norepinephrine release from the amygdala of rats exposed to 20 min restraint stress closely matches that of CRF-IR described in the present work. In vitro norepinephrine evokes CRF-IR release from hypothalamic neurons (Tsagarakis et al, 1988;Hu et al, 1992), while microdialysis experiments show that CRF produces norepinephrine release from nerve terminals in prefrontal cortex and hypothalamus (Lavicky and Dunn, 1993), suggesting the existence of a reciprocal stimulating interaction between CRF and norepinephrine. Although the relevance of central norepinephrine in anxiety is still under debate, some of the behavioral effects produced by stress and ethanol withdrawal involve adrenoreceptor mediation (Berridge and Dunn, 1989;Glue et al, 1989;Soderpalm and Engel, 1990).…”