Depletion of brain serotonin by 5,7-DHT: effects on the 8-OH-DPAT-induced changes of sleep and waking in the rat.
The effect of 5-HT1A receptor agonist 8-OH-DPAT on sleep and wakefulness was studied in rats with selective serotonin depletion after ICV administration of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT). Injection of 8-OH-DPAT to vehicle-treated animals induced biphasic effects, such that low doses (0.010 mg/kg) which act perferentially on the somatodendritic autoreceptor decreased wakefulness (W) and increased slow wave sleep (SWS), while higher doses (0.375 mg/kg) which stimulate postsynaptic receptors caused opposite effects. REM sleep was suppressed irrespective of the dosage given. Injection of the 0.010 mg/kg dose in the 5,7-DHT-treated rats did not result in significant changes in sleep or W. On the other hand, the 0.375 mg/kg dose produced changes in sleep variables which were similar to those described in the vehicle-treated animals. Our findings tend to indicate that increased SWS after low doses of 8-OH-DPAT depends upon the activation of inhibitory somatodendritic 5-HT1A receptors, while increased W after higher doses of the compound is related to stimulation of postsynaptic receptors.
Monti
J M
JM
Department of Pharmacology and Therapeutics, School of Medicine, Clinics Hospital, Montivideo, Uruguay.
Jantos
H
H
Silveira
R
R
Reyes-Parada
M
M
Scorza
C
C
Prunell
G
G
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology*; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017661:Receptors, Presynaptic / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism* / Q000502:physiology; D012890:Sleep / Q000187:drug effects*; D012895:Sleep, REM / Q000187:drug effects; D014851:Wakefulness / Q000187:drug effects*
D015306:Biogenic Monoamines; D017661:Receptors, Presynaptic; D011985:Receptors, Serotonin; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin