Decline in serotonergic firing activity and desensitization of 5-HT1A autoreceptors after chronic unpredictable stress.
Chronic stressful life events are risk factors for contracting depression, the pathophysiology of which is strongly associated with impairments in serotonergic (5-HT) neurotransmission. Indeed, in rodents, exposure to chronic unpredictable stress (CUS) produces depressive-like behaviours such as behavioural despair and anhedonia. To date, there have not been many studies that especially explore in vivo changes in 5-HT neurotransmission associated with CUS in the rat. Therefore, using in vivo electrophysiology, we evaluated whether CUS that induces anhedonia-like behaviours concurrently impairs midbrain raphe 5-HT neuronal activity. Unlike unstressed and acutely stressed rats, CUS produced progressive reductions in sucrose intake and preference (anhedonia-like). These were associated with a decrease in the spontaneous firing activity (35.4%) as well as in the number of spontaneously active 5-HT neurons, and a desensitization of somatodendritic 5-HT1A autoreceptors in the dorsal raphe. These results suggest that CUS dramatically decreases 5-HT neural activity and 5-HT1A autoreceptor sensitivity, and may represent endophenotypic features of depressive-like states.
Bambico
Francis Rodriguez
FR
Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montréal, QC, Canada.
Nguyen
Nhu-Tram
NT
Gobbi
Gabriella
G
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D004347:Drug Interactions; D004558:Electric Stimulation; D005518:Food Preferences / Q000187:drug effects; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013315:Stress, Psychological / Q000378:metabolism* / Q000473:pathology; D013395:Sucrose / Q000008:administration & dosage; D013549:Sweetening Agents / Q000008:administration & dosage; D013997:Time Factors
D010879:Piperazines; D011725:Pyridines; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013549:Sweetening Agents; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D013395:Sucrose; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin