Role of serotonin-1A receptors in restraint-induced behavioral deficits and adaptation to repeated restraint stress in rats.
8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), a selective 5-hydroxy-tryptamine (5-HT; serotonin)-1A agonist was used to evaluate the role 5-HT-1 A receptors in restraint-induced behavioral deficits and adaptation to repeated restraint stress in rats. Animals were injected with 8-OH-DPAT at a dose of 0.25 mg/kg 1 h before exposing to an episode of 2 h/day restraint stress daily for 5 days. Effects of drug administration and restraint stress on 24 h cumulative food intakes were monitored daily. Intensity of 8-OH-DPAT-induced serotonin syndrome was also monitored each day before submitting animals to the episode of stress. Exposure to the first episode of 2 h restraint stress resulted in a decrease in 24 h cumulative food intake and an attenuation of 8-OH-DPAT-induced serotonin syndrome monitored next day. The deficits attenuated following 2nd and 3rd 2 h/day restraint were not observed following the 4th and 5th 2 h/day restraint. The decreases of food intake following 1st and 2nd day restraint sessions were smaller in 8-OH-DPAT than saline-injected animals. Administration of 8-OH-DPAT on day 6 elicited comparable serotonin syndrome in unrestrained and repeatedly restrained groups. Brain 5-HT metabolism decreased in unrestrained but not repeatedly restrained animals. The results suggest that a decrease in serotonergic neurotransmission is involved in restraint-induced behavioral deficits while a normalization of serotonin neurotransmission due to desensitization of somatodendritic 5-HT-1A receptors may help cope with the stress demand to produce adaptation to stress.
Haleem
Darakhshan J
DJ
Department of Biochemistry, Neurochemistry and Biochemical Neuropharmacology, Research Laboratory, University of Karachi, Karachi, Pakistan. djh@super.net.pk
Samad
Noreen
N
Perveen
Tahira
T
Haider
Saida
S
Haleem
M A
MA
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000008:administration & dosage; D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001526:Behavioral Symptoms / Q000209:etiology* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D012149:Restraint, Physical / Q000379:methods*; D012701:Serotonin / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage; D013315:Stress, Psychological / Q000150:complications*
D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin