Effects of serotonin on perifornical-lateral hypothalamic area neurons in rat.
The hypocretin (HCRT) system of the perifornical-lateral hypothalamic area (PF-LHA) has been implicated in the facilitation of behavioral arousal. HCRT neurons receive serotonergic afferents from the dorsal raphe nucleus. Although in-vitro pharmacological studies suggest that serotonin (5-HT) inhibits HCRT neurons, the in-vivo effects of 5-HT on HCRT neurons in the PF-LHA and associated behavioral changes have not been described. We examined the effects of 5-HT delivered locally into the PF-LHA using reverse microdialysis on its neuronal activity and the consequent sleep-wake changes in rats. First, we quantified Fos expression (Fos-IR) in HCRT and other PF-LHA neurons following unilateral 5-HT perfusion in awake rats. Second, we determined the transient effects of 5-HT perfusion on the extracellular activity of the PF-LHA neurons recorded via microwires placed adjacent to the microdialysis probe. Third, we examined the effects of 5-HT perfusion into the PF-LHA on the sleep-wake profiles of the rats during the lights-off period. Unilateral perfusion of 5-HT into the PF-LHA in awake rats dose-dependently decreased the number of HCRT neurons exhibiting Fos-IR. 5-HT also inhibited the discharge activity of four of five responsive wake-related, putative HCRT neurons. However, unilateral perfusion of 5-HT into the PF-LHA did not produce significant behavioral changes during the 2-h recording period. These results confirm the in-vitro findings that 5-HT exerts inhibitory influences on HCRT neurons but further suggest that the inactivation of a limited number of HCRT neurons by unilateral 5-HT microdialysis may not be sufficient to induce behavioral changes.
Kumar
Sunil
S
Research Service (151A3), Veteran Affairs Greater Los Angeles Healthcare System, 16111 Plummer Street, Sepulveda, California 91343, USA.
Szymusiak
Ronald
R
Bashir
Tariq
T
Rai
Seema
S
McGinty
Dennis
D
Alam
Md Noor
MN
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D004576:Electromyography / Q000379:methods; D007839:Functional Laterality; D005786:Gene Expression Regulation / Q000187:drug effects; D007026:Hypothalamic Area, Lateral / Q000166:cytology*; D007150:Immunohistochemistry / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008543:Melanins / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D009479:Neuropeptides / Q000378:metabolism; D016761:Oncogene Proteins v-fos / Q000378:metabolism; D000068797:Orexins; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology*; D012890:Sleep / Q000187:drug effects / Q000502:physiology; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology
D047908:Intracellular Signaling Peptides and Proteins; D008543:Melanins; D009479:Neuropeptides; D016761:Oncogene Proteins v-fos; D000068797:Orexins; D012701:Serotonin