Behavioral, Physiological, and Neuroendocrine Stress Responses and Differential Sensitivity to Diazepam in Two Wistar Rat Lines Selectively Bred for High- and Low-Anxiety–Related Behavior

• Published in: Neuropsychopharmacology (New York, N.Y.) Vol. 19; no. 5; pp. 381 - 396
• Main Authors: Liebsch, Gudrun, Linthorst, Astrid C.E., Neumann, Inga D., Reul, Johannes M.H.M., Holsboer, Florian, Landgraf, Rainer
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-11-1998; Nature Publishing
• Subjects: Adrenocorticotropic Hormone - blood; Adult and adolescent clinical studies; Animals; Anti-Anxiety Agents - pharmacology; Anxiety - genetics; Anxiety disorders. Neuroses; Benzodiazepines; Biological and medical sciences; Biotelemetry; Corticosterone - blood; Diazepam - pharmacology; Emotionality; Forced swim test; HPA system, Elevated plus-maze; Male; Medical sciences; Miscellaneous; Motor Activity - drug effects; Neuropharmacology; Pharmacology. Drug treatments; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Rats; Rats, Wistar; Stress coping; Stress, Physiological - blood; HPA system, Elevated plus-maze; Emotionality; Stress coping; Forced swim test; Biotelemetry; Benzodiazepines; Intraperitoneal administration; Rat; Hypothalamohypophysoadrenal axis; Corticosterone; Psychotropic; Peptide hormone; Anxiety disorder; ACTH; Genetic determinism; Glucocorticoid; Type specificity; Benzodiazepine derivatives; Genetics; Anxiety; Coping; Diazepam; Pathophysiology; Steroid hormone; Rodentia; Biological activity; Stress; Vertebrata; Mammalia; Tranquillizer; Adenohypophyseal hormone; Animal; Adrenal hormone
• ISSN: 0893-133X; 1740-634X
• DOI: 10.1016/S0893-133X(98)00042-6

Two Wistar rat lines, selectively bred for high-anxiety–related behavior (HAB) and low-anxiety–related behavior (LAB) in the elevated plus-maze test, were tested for the susceptibility of their behavioral characteristics to anxiolytic treatment and for their endocrine and physiological reactivity to different stressors. Injection of 1mg/kg diazepam failed to affect line differences in coping strategy but resulted in a marked (20-fold) decrease in plus-maze anxiety in HAB rats; whereas, the anxiolytic effect was less pronounced in LAB animals. Biotelemetrical measurements revealed that HAB and LAB rats do not significantly differ in their baseline body temperature, locomotor activity, food and water intake, or in stress-induced alterations of the diurnal rhythms in these parameters. However, line differences were found in acute changes in body temperature and locomotor activity following stress exposure, LAB rats responding with a greater, albeit shorter, increase in body temperature and activity than HAB animals. Basal ACTH and corticosterone plasma levels as well as pituitary reactivity to intravenously administered CRH (40 ng/kg) were similar in both lines, although, especially in response to plus-maze exposure, HAB rats tended toward higher ACTH secretion than LAB rats. These data confirm that animals with high or low basal levels of anxiety may be a promising model for studying the mechanisms of action of anxiolytic substances. Nevertheless, the endocrine findings support the notion that the reactivity of the hypothalamo-pituitary-adrenocortical system and anxiety-related behavior can be regulated independently.