Acute modulation of somatostatin receptor function by melatonin in the ratfrontoparietal cortex

Since melatonin (N-acetyl-5-methoxytryptamine) decreases locomotor activity and rearing and increases grooming behavior in a similar manner as somatos tatin (SRIF), we examined if melatonin could induce these changes through s omatostatinergic neurotransmission in the rat frontoparietal cortex. Male W istar rats (200-250 g) received a single injection of melatonin (25 mug/kg per day) subcutaneously (s.c.) and were sacrificed 5 hr later. Melatonin tr eatment increased the number of I-125-Tyr(11)-SRIF receptors in frontoparie tal cortical membranes without any changes in the dissociation constant (K- d). The capacity of SRIF to inhibit basal and forskolin (FK)-stimulated ade nylyl cyclase (AC) activity was increased in melatonin-treated rats as comp ared to the control animals. Melatonin administration also induced a lower AC activity, both under basal conditions and after stimulation of the enzym e via stimulatory guanine nucleotide-binding proteins (Gs), or directly wit h FK. Functional inhibitory guanine nucleotide-binding protein (Gi) activit y was increased in frontoparietal cortical membranes from melatonin-treated rats when compared to controls. Western blot analyzes showed that melatoni n administration did not alter the amount of the Gi alpha (1) or Gi alpha ( 3) subunits, but reduced Gi alpha (2) levels in frontoparietal cortical mem branes. No significant changes in SRIF-like immunoreactivity content and SR IF mRNA levels were detected in this brain area after melatonin treatment. Administration of the melatonin receptor antagonist luzindole (10 mg/kg, s. c.) 30 min before melatonin injection did not change the melatonin-induced effects on the SRIF receptor-effector system. In conclusion, the present re sults show that acute melatonin administration increases the activity of th e SRIF receptor-effector system and decreases Gi alpha (2) levels in the ra t frontoparietal cortex. In addition, the coupling of Gs to AC is disturbed by melatonin.