Long-lasting effects of an acute stress on the neurochemistry and function of 5-hydroxytryptaminergic neurones in the mouse brain.
The present experiments investigated the effects of a novel stress challenge (6-min swim test) on behaviour (immobility) and the neurochemistry of cortical 5-hydroxytryptaminergic neurones in CD1 mice. The influence of previous experience of stress (once-daily saline injection) or administration of the noradrenaline and 5-hydroxytryptamine (5-HT) uptake blocker, sibutramine hydrochloride, on any changes was also evaluated. 5-HT2A receptor binding was unchanged 24 h after the last injection of either saline or sibutramine alone but immobility in the swim test was reduced to the same extent by these pretreatments. Seven days, but not 3 h, after the swim test, the density of 5-HT2A receptors and the frequency of 5-HT2A receptor-mediated head-twitches were increased significantly. These increases were prevented by saline injection, but sibutramine prevented the increase in head-twitches only. Sibutramine, but not saline, reduced 5-HT synthesis and 5-HT2A receptor-mediated head-twitches 3 h after the swim and increased synthesis at 7 days. The results indicate that a brief stress can have long-term effects on central 5-hydroxytryptaminergic neurones. Previous experience of stress or sibutramine has marked, but dissimilar, effects on these changes. These findings might be relevant to long-lasting CNS disorders provoked, or aggravated, by stress.
Davis
S
S
Department of Pharmacology, University College London, UK.
Heal
D J
DJ
Stanford
S C
SC
D006916:5-Hydroxytryptophan / Q000378:metabolism; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D003503:Cyclobutanes / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000502:physiology*; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000378:metabolism*; D013997:Time Factors
D000928:Antidepressive Agents; D003503:Cyclobutanes; D011985:Receptors, Serotonin; D006916:5-Hydroxytryptophan; C058254:sibutramine