Abstract
The role of corticotropin-releasing factor (CRF) in mediating the stress response was studied using a behavioral test in which anxiety or conflict influence performance. Rats implanted with intraventricular cannulae were tested in a Geller-Seifter conflict test modified for incremental shock. CRF produced a dose-dependent attenuation of punished and nonpunished responding in the conflict test. Chlordiazepoxide increased punished, but not unpunished, responding and produced a dose-dependent reversal of CRF-induced response suppression. CRF had no effect on tail flick or hot-plate analgesia tests. The results support the hypothesis that CRF produces behavioral effects consistent with “anxiety” or an increased responsiveness to stress.
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Barlow SM, Knight AF, Sullivan FM (1979) Plasma corticosterone response to stress following chronic oral administration of diazepam in the rat. J Pharm Pharmacol 31:23–26
Benson H, Herd J, Morse W, Kelleher R (1970) Hypotensive effects of chlordiazepoxide, amobarbital and chlorpromazine on behaviorally induced elevated blood pressure in the squirrel monkey. J Pharmacol Exp Ther 173:399–406
Britton DR, Britton KT (1981) A sensitive open field measure of anxiolytic drug activity. Pharmacol Biochem Behav 15:577–582
Britton DR, Koob GF, Rivier J, Vale W (1982) Intraventricular corticotropin-releasing factor enhances behavioral effects of novelty. Life Sci 31:363–367
Britton KT, Stewart RD, Risch SC (1983) Benzodiazepines attenuate stimulated β-endorphin release. Psychopharmacol Bull 19:757–760
Brown MR, Fisher LA, Rivier J, Spiess J, Rivier C, Vale W (1982) Cortiocotropin-releasing factor: effects on the sympathetic nervous system and oxygen consumption. Life Sci 30:207–210
Camoratto AM, Grandison L (1983) Inhibition of cold-induced TSH release by benzodiazepines. Brain Res 265:339–343
Cook L, Sepinwall J (1975) Behavioral analysis of the effects and mechanism of action of the benzodiazepines. In: Costa E, Greengard P (eds) Mechanism of action of benzodiazepines. Raven, New York, pp 1–28
Dasgupta S, Mukherjee B (1967) Effect of chlordiazepoxide on stomach ulcers in rabbits induced by stress. Nature 215:1183
De Wied D (1980) Pituitary adrenal system hormones and behavior. In: Seyle H (ed), Selye's guide to stress research, vol 1. New Van Nostrand Reinhold, pp 252–279
File S (1979) Effects of ACTH4–10 in the social interaction test of anxiety. Brain Res 171:157–160
Ford RD, Rech RH, Commissaris RL, Meyer LY (1979) Effects of acute and chronic interactions of diazepam and d-amphet-amine on punished behavior in rats. Psychopharmacology 65:197–204
Gerhardt S, Liebman JM (1983) Effects of antidepressants, anxiogenic substances and benzodiazepine antagonists on the self-regulation of ICSS duration. Soc Neurosci Abstr 9:436
Grandison L (1982) Suppression of prolactin secretion by benzodiazepines in vivo. Neuroendocrinology 34:369–373
Kilts CD, Commissaris RL, Rech RH (1981) Comparison of anticonflict drug effects in three experimental models of anxiety. Psychopharmacology 74:290–296
Kilts CD, Commissaris RL, Cordon JJ, Rech RH (1982) Lack of central 5-hydroxytryptamine influence on the anticonflict activity of diazepam. Psychopharmacology 78:156–164
Koob GF (1984) Stress, corticotropin-releasing factor, and behavior. In: Williams RM (ed) Perspectives on behavioral medicine: Neuroendocrine control and behavior. Academic, New York
Lahti RA, Barsuhn C (1975) The effect of various doses of minor tranquilizers on plasma corticosteroids in stressed and non-stressed rats. Res Commun Chem Pathol Pharmacol 11: 595–603
Levine AS, Rogers B, Kneip J, Grace M, Morley JE (1983) Effect of centrally administered corticotropin-releasing factor (CRF) on multiple feeding paradigms. Neuropharmacology 22:337–339
Marki W, Spiess J, Tache Y, Brown M, Rivier J (1981) Total solid phase synthesis of porcine gut gastrin releasing peptide (GRP), a mammalian bombesin. J Am Chem Soc 103: 3178–3185
Morley JE, Levine AS (1982) Corticotropin-releasing factor, grooming and ingestive behavior. Life Sci 31:1459–1464
O'Callaghan J, Holtzman S (1975) Quantification of the analgesic activity of narcotic antagonists by a modified hot plate procedure. J Pharmacol Exp Ther 192:497–505
Peterfreund RA, Vale W (1983) Ovine corticotropin-releasing factor stimulates somatostatin secretion from cultured brain cells. Endocrinology 112:1275–1278
Proulx-Ferland S, Labrie F, Dumont D, Cote J, Coy D, Sveiraf J (1982) Corticotropin-releasing factor stimulates secretion of melanocyte-stimulating hormone from the rat pituitary. Science 217:62–63
Rivier C, Brownstein M, Spiess J, Rivier J, Vale W (1981) In vivo corticotropin-releasing factor-induced secretion of adreno-corticotropin, β-endorphin and corticosterone. Endocrinology 110:272–278
Rivier J, Spiess J, Rivier C, Galyean R, Vale W, Lederis K (1983) Solid phase synthesis of amunine (CRF), sauvagine, and two urotensin. In: Blaha K, Malon P (eds) Peptides, 1982. de Gruyler, Berlin, pp 597–602
Sutton RE, Koob GF, LeMoal M, Rivier J, Vale W (1982) Corticotropin-releasing factor produces behavioral activation rats. Nature 297:331–333
Torellas A, Guaza C, Borrell J (1980) Effects of acute and pro-longed administration of chlordiazepoxide upon the pituitary-adrenal activity and brain catecholamines in sound stressed and unstressed rats. Neuroscience 5:2289–2295
Vale W, Spiess J, Rivier C, Rivier J (1981) Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and β-endorphin. Science 213:1394–1397
Vellucci S, Webster R (1982) Antagonism of the anticonflict effects of chloradiazepoxide by β-carboline carboxylic acid ester, Ro 15-1788 and ACTH(4–10). Psychopharmacology 78:256–260
Winer BJ (1971) Statistical principles in experimental design. McGraw-Hill, New York
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Britton, K.T., Morgan, J., Rivier, J. et al. Chlordiazepoxide attenuates response suppression induced by corticotropin-releasing factor in the conflict test. Psychopharmacology 86, 170–174 (1985). https://doi.org/10.1007/BF00431704
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DOI: https://doi.org/10.1007/BF00431704