Involvement of hypothalamic corticotropin-releasing factor neurons in behavioral responses to novelty in rats

doi:10.1016/0304-3940(94)90435-9

Neuroscience Letters

Volume 168, Issues 1–2, 28 February 1994, Pages 139-142

https://doi.org/10.1016/0304-3940(94)90435-9 Get rights and content

Abstract

The purpose of this experiment was to investigate whether endogenous corticotropin-releasing factor (CRF) within the paraventricular nucleus of the hypothalamus (PVN) is involved in the alteration of locomotor activity related to a novel, presumably stressful, environment in rats. Impairment of the function of CRF-containing neurons was effected by immunotargeting ricin A chain toxin to these cells with a monoclonal antibody to CRF (CRF-MAb/toxins). CRF-MAb/toxins administered into the PVN 2 weeks prior to testing produced an increase in locomotor activity during exposure to novel environment photocell cages. This behavioral activation was maintained throughout the 120 min experimental session, but was not present when the rats where introduced to the same photocell cages after extensive habituation. These results suggest that the effect induced by CRF-MAb/toxin treatment was related to the exploration of the novel environment, and was not due to a generalized locomotor hyperactivity. This effect was accompanied by a 53% and 61% CRF decrease in the hypothalamus and the median eminence, respectively. Injection of CRF-MAb/toxins into the ventromedial nucleus of the hypothalamus did not modify the locomotor activity in either unfamiliar or familiar conditions. These data suggest that CRF neurons within the PVN may participate not only in the activation of the pituitary adrenal axis associated with stressors but also as physiological mediators of the behavioral responses to stress.

References (24)

D.R. Britton et al.
Intraventricular Corticotropin-releasing factor enhances behavioral effects of novelty
Life Sci.
(1982)
Y. Endo et al.
RNA N-glycosidase activity of ricin A-chain
Mechanism of action of the toxic lectin ricin on eukaryotic ribosomes
J. Biol. Chem.
(1987)
J.P. Herman et al.
Lesions of parvocellular subdivisions of the hypothalamic paraventricular nucleus alter open field behavior and acquisition of sensory and spatial discrimination
Brain Res.
(1991)
D.D. Krahn et al.
Behavioral effects of corticotropin-releasing factor: localization and characterization of central effects
Brain Res.
(1988)
F. Menzaghi et al.
Alteration of pituitary-adrenal responses to adrenalectomy by the immnulogical targeting of CRF neurons
Neurosci. Lett.
(1992)
F. Menzaghi et al.
Functional impairment of hypothalamic corticotropin-releasing factor neurons with immunotargeted toxins enhances food intake induced by neuropeptide Y
Brain Res.
(1993)
H. Monnikes et al.
CRF in the paraventricular nucleus of the hypothalamus induces dose-related behavioral profile in rats
Brain Res.
(1992)
P.E. Sawchenko
Evidence for differential regulation of corticotropin-releasing factor and vasopressin immunoreactivities in parvocellular neurosecretory and autonomic-related projections of the paraventricular nucleus
Brain Res.
(1987)
D.R. Britton et al.
Central effects of corticotropin releasing factor (CRF): Evidence for similar interactions with environmental novelty and with caffeine
Psychopharmacology
(1990)
Brown, M. and Fisher, L.A., Regulation of the autonomic nervous system by corticotropin releasing factor. In E. B. De...

T.O. Bruhn et al.

Effects of paraventricular lesions on corticotropin-releasing factor (CRF)-like immunoreactivity in the stalk-median eminence: studies on the adrenocorticotropin response to ether stress and exogenous CRF

Endocrinology

(1984)

P.D. Butler et al.

Corticotropin-releasing factor produces fear-enhancing and behavioral activating effects following infusion into the locus coeruleus

J. Neurosci.

(1990)

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Involvement of hypothalamic corticotropin-releasing factor neurons in behavioral responses to novelty in rats

Abstract

Life Sci.

J. Biol. Chem.

Brain Res.

Brain Res.

Neurosci. Lett.

Brain Res.

Brain Res.

Brain Res.

Central effects of corticotropin releasing factor (CRF): Evidence for similar interactions with environmental novelty and with caffeine

Psychopharmacology

Effects of paraventricular lesions on corticotropin-releasing factor (CRF)-like immunoreactivity in the stalk-median eminence: studies on the adrenocorticotropin response to ether stress and exogenous CRF

Endocrinology

Corticotropin-releasing factor produces fear-enhancing and behavioral activating effects following infusion into the locus coeruleus

J. Neurosci.