Effects of Alpha-Flupenthixol and Naloxone on CRF-Induced Locomotor Activation

Abstract

Corticotropin-releasing factor injected intracerebroventricularly in a dose of 1 µg produced a prolonged locomotor activation (3 h) in rats previously habituated to the test cage environment. This activation was reversed by α-flupenthixol (intraperitoneally), a dopamine receptor antagonist, only at cataleptic doses and not at all by naloxone (subcutaneously) in doses of 0.02–5.0 mg/kg. The effective dose 50% (ED₅₀) for the α-flupenthixol reversal of locomotor activity induced by corticotropin-releasing factor was 0.13 mg/kg; similar to the 0.14 mg/kg ED₅₀ needed to reverse the locomotor activation produced by caffeine (10 mg/kg s.c). The ED₅₀ necessary to reverse amphetamine (0.75 mg/kg s.c.) locomotion with this drug was 0.07 mg/kg. The results suggest that the corticotropin-releasing factor acts independently of direct activation of the dopamine or opioid peptide systems.

Corticotropin-Releasing Factor in the Norepinephrine Nucleus, Locus Coeruleus, Facilitates Behavioral Flexibility

“…Intracerebroventricular CRF elicits active behaviors including increased locomotor activity in a familiar environment, grooming, burying, and aggressive behaviors (Eaves et al, 1985;Howard et al, 2008;Koob et al, 1984;Sutton et al, 1982;Tazi et al, 1987). In certain rodent models, CRF has anxiogenic effects expressed as effects in the elevated plus maze, enhanced conditioned freezing, decreased activity in open field, potentiated startle, and decreased punished responding Cole and Koob, 1988;De Boer et al, 1992;Liang et al, 1992).…”

Neuropeptidergic Mediators of Spontaneous Physical Activity and Non-Exercise Activity Thermogenesis

“…Effects of CRH on SPA are also well documented but the mechanism(s) underlying its effect on SPA are less well understood. ICV [62,63,64,65] and site-specific [66,67,68,69,70,71,72] CRH administration increases SPA. However, no effect of CRH was shown after injection into the LC [73], core of the NAcc [67] or the lateral hypothalamus (LH) [70].…”

Impaired diurnal adrenal rhythmicity restored by constant infusion of corticotropin-releasing hormone in corticotropin-releasing hormone-deficient mice.

“…To determine if CRH KO mice lack other circadian rhythms besides that in pituitary-adrenal function, we analyzed locomotor activity. CRH, outside the paraventricular nucleus of the hypothalamus, is synthesized in many regions of the cerebral cortex and brainstem (35), where it is believed to impart stress-related behaviors (36,37). To assess the role of CRH in the generation of circadian behavior, wheel running was first monitored under conditions of a fixed LD cycle (14:10 LD).…”