Chronic melatonin treatment reverses disruption of prepulse inhibition in pinealectomized and pinealectomized-plus-ovariectomized rats.

Although melatonin has been implicated in several neurophysiological systems, data on the relationship of melatonin with psychosis such as schizophrenia are limited and contradictory. Chronic effects of melatonin on sensorimotor gating deficits have also not been investigated yet. We investigated the neurobehavioral effects of chronic administration of melatonin in pinealectomized (Px) and ovariectomized (Ovx) rats. Px or Ovx or both operations were carried out together to the rats. The control group of rats was sham operated. A sham ovariectomy was carried out to Px rats, and vice versa. Fifth month later, melatonin (5mg/kg) or vehicle was injected to rats for 28 days. Then, prepulse inhibition (PPI) of acoustic startle reflex, startle amplitude and startle reflex latency was measured. Locomotor activity, accelerod performance measurements, novel object recognition and passive avoidance tests were also evaluated. Px and Px+Ovx rats had impaired PPI compared to control rats. Melatonin reversed the impairments of PPI induced by Px or Px+Ovx. While melatonin treatment had no effect on locomotor activity of control rats, it significantly increased the locomotor activity of Px and Px+Ovx rats. Melatonin treatment (5mg/kg/day, 28 days) reversed the locomotor hyperactivity caused by Ovx. Accelerod performance, passive avoidance, and object recognition responses of Px, Ovx or Px+Ovx rats were not different from the control group. Our results indicate that chronic melatonin deficiency by reason of Px results in impairment of PPI reflex and replacement of melatonin exerts beneficial effects on the impaired PPI reflex in Px and Ovx rats. Thus, melatonin may be useful in the treatment of some disorders characterized by sensorimotor gating deficits such as schizophrenia.

The role of nitric oxide in the effects of ovarian steroids on spontaneous myometrial contractility in rats.

Forty ovariectomized rats were apportioned into one control and three experimental groups (n=10 each) to evaluate the role of nitric oxide in the effects of ovarian steroids on spontaneous myometrial contractility in rats. The control group (group Ov) received sesame oil once daily for 10 days, whereas rats in the experimental groups were treated with progesterone (2 mg/(rat day); group P), 17beta-estradiol (10 microg/(rat day); group E2), or progesterone and 17beta-estradiol together (group E2+P). The functionality of the arginine-nitric oxide synthase (NOS)-nitric oxide (NO) pathway in the uterine horns of sacrificed rats was evaluated in an isolated organ bath. L-Arginine, sodium nitroprusside (SNP) and 8-Br-cGMP decreased uterine contractile tension induced by electric field stimulation (EFS) in the Ov, P, and E2+P groups, but not in the E2 group. In addition, L-arginine was ineffective when applied together with a NOS inhibitor, L-nitro-N-arginine (L-NNA). The percentage of contractile inhibition was higher in the Ov and P groups compared to the E2+P group. Immunohistochemical evaluation revealed that expression of neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS) in smooth muscles and nerve cells did not differ among the groups. Expression of nNOS and eNOS was strongly evident in the E2 and E2+P groups at both surface and glandular epithelium of the endometrium. iNOS expression was increased in surface epithelium of the E2 and E2+P groups. However, iNOS expression was only increased in glandular epithelial cells of the E2+P group. In conclusion, the L-arginine-NOS-NO pathway inhibits myometrial contractions via cGMP-dependent and -independent mechanisms, and while progesterone maintains the nitric oxide effects, estrogen prevents them. These results suggest that NOS does not mediate the effects of estrogen.