Long-Term Cortisol Treatment Impairs Behavioral and Neuroendocrine Responses to 5-HT1 Agonists in the Rat
- 1 January 1989
- journal article
- research article
- Published by S. Karger AG in Neuroendocrinology
- Vol. 50 (3), 241-247
- https://doi.org/10.1159/000125248
Abstract
The effects of chronic cortisol treatment on neuroendocrine and behavioral responses to serotonim (5-HT1) receptor agonists were studied in conscious, freely moving rats. Seven-day cortisol treatment (25 mg/kg/day with osmotic minipumps) markedly suppressed basal plasma corticotropin (ACTH) and corticosterone concentrations, indicating a suppression of the hypothalamo-pituitary-adrenocortical axis. Cortisol also decreased body weight, food intake, plasma norepinephrine (NE), and epinephrine (E) levels. In the drug challenge studies, we used two 5-HTι agonists, the 5-HT1B and 5-HT1C agonist, m-chlorophenylpiperazine (m-CPP), and the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OHDPAT), to examine the effect of cortisol on their behavioral and neuroendocrine effects. After 7-day cortisol treatment, plasma prolactin responses to both m-CPP and 8-OHDPAT were significantly decreased. While the plasma NE, E, and food intake responses to m-CPP were also significantly reduced by cortisol treatment, these same responses to 8-OHDPATwere unchanged. The effect of m-CPP on locomotor activity was also decreased. Since only the responses to m-CPP and 8-OHDPAT previously shown to be antagonized by pretreatment with the 5-HT1/5-HT2 antagonist, metergoline, were significantly attenuated after cortisol treatment, these changes may be specific to 5-FΓT receptors. These data indicate that chronic exposure to high glucocorticoid levels alters 5-HT1 receptor-mediated functions and provides additional evidence relevant to the contribution of glucocorticoid elevation to the symptoms of depression.Keywords
This publication has 10 references indexed in Scilit:
- The serotonin agonist, M-chlorophenyl-piperazine, markedly increases levels of plasma catecholamines in the conscious ratNeuropharmacology, 1988
- Food intake, neuroendocrine and temperature effects of 8-OHDPAT in the ratEuropean Journal of Pharmacology, 1988
- Further studies of the putative serotonin agonist, m-chlorophenylpiperazine: Evidence for a serotonin receptor mediated mechanism of action in humansPsychopharmacology, 1986
- 5-HT-la and 5-HT-lb selectivity of two phenylpiperazine derivatives: Evidence for 5-HT-lb heterogeneityLife Sciences, 1985
- Corticosterone modulation of neurotransmitter receptors in rat hippocampus: A quantitative autoradiographic studyBrain Research, 1985
- Neuroendocrine and behavioral effects of m-chlorophenylpiperazine administration in rhesus monkeysLife Sciences, 1983
- Long term acth induced diminished responsiveness of prolactin secretion to morphineLife Sciences, 1983
- A Specific Laboratory Test for the Diagnosis of MelancholiaArchives of General Psychiatry, 1981
- m-Chlorophenylpiperazine: A central serotonin agonist causing powerful anorexia in ratsNaunyn-Schmiedebergs Archiv für experimentelle Pathologie und Pharmakologie, 1979
- Presentation of the Steroid PsychosesJournal of Nervous & Mental Disease, 1979