Anxiolytic-like actions of melatonin, 5-metoxytryptophol, 5-hydroxytryptophol and benzodiazepines on a conflict procedure.

Male Wistar rats (120-230 g) were used in these experiments. Some rats were deprived of water for 48 h before testing in a conflict procedure. Then, after 20 licks from a water bottle with a metal drinking tube, the animal received an electric shock (0.5 mA/500 msec). The effects of two classical anxiolytic drugs, DIAZ (1.0, 2.0 and 4.0 mg/Kg b.wt), and CDP (5.0 and 10.0 mg/Kg b.wt) were compared to those produced by MEL (0.1, 0.2, 0.5, 1.0 and 2.0 mg/Kg b.wt), 5-MTOPHOL (1.0 and 2.0 mg/Kg b.wt), 5-HTOPHOL (1.0 and 2.0 mg/Kg b.wt) and vehicle solution. Anxiolytic drugs as well as MEL produced a dose-dependent increase in the number of shocks received. The results suggest that the three pineal indoles are involved in the modulation of the stress responses. MEL showed a higher potency than the other indoles.

Apamin blocks the direct relaxant effect of melatonin on rat ileal smooth muscle.

The present study investigated the mechanisms of melatonin-induced inhibition of the ileal smooth muscle contraction. Rat isolated ileal smooth muscle strips were stimulated in an organ bath using carbachol (CAR) or potassium chloride (KCl) depolarization. Under these conditions, melatonin produced a concentration-dependent inhibition of muscle contraction (mean inhibitory concentration, IC50: 17.3 x 10(-6) M), which was not blocked by either tetrodotoxin (10(-6) M), hexamethonium (10(-4) M), or phentolamine (10(-6) M). The inhibitory effect of melatonin during CAR stimulation was blocked in a concentration-dependent manner by the presence of apamin (4.8 x 10(-9) M), a K(+)-channel blocker. By contrast, other K(+)-channel blockers such as 4-aminopyridine (10(-4) M to 5 x 10(-3) M), tetraethylammonium (10(-4) to 10(-1) M), and glibenclamide (10(-5) M) were ineffective. Additionally, the Ca(2+)-channel antagonists nitrendipine (IC50: 2.4 x 10(-9) M) and verapamil (IC50: 1.1 x 10(-7) M) also blocked the inhibitory action of melatonin. These results suggest that melatonin may interact with an apamin-sensitive, possibly Ca(2+)-activated, K+ channel and thus cause an inhibition of ileal smooth muscle contractions.

Melatonin modifies the spontaneous multiunit activity recorded in several brain nuclei of freely behaving rats.

Melatonin, a pineal hormone, released photoperiodically, was administered systemically in rats, previously implanted with semimicroelectrodes into six different brain structures. The multiunit electrical activity of these structures was recorded for 10 min before and 60 min after melatonin administration in unanesthetized, freely moving rats. Different melatonin doses (100, 200, 500, and 1000 micrograms/kg) produced changes in the electrical activity of all tested structures. However, amygdala, rostral hypothalamus and mesencephalic reticular formation showed the most important changes. The main effect induced by melatonin was a dose-related decrease of the spontaneous electrical activity. The significance of these effects is discussed within the context of the behavioral and endocrinological effects of melatonin.