Electrical responses of pineal cells to melatonin and putative transmitters. Evidence for circadian changes in sensitivity.

The effects of microelectrophoretically applied melatonin (N-acetyl-5-methoxy-tryptamine), noradrenaline (NOR) or acetylcholine (ACH) on the electrical activity of pineal cells during both the day- and night-time were studied in urethane anesthetised guinea-pigs. A total of 288 cells were tested with melatonin, and in addition with either NOR (120 cells) or ACH (138 cells). Of the 206 cells responding to melatonin application, 139 were excited and 67 inhibited. A total of 85 cells responded to the application of NOR, 45 being excited and 40 inhibited. Responses to ACH application were observed in 75 pineal cells, 49 units being inhibited and 26 excited. It was possible to observe excitation in 18 units following electrical stimulation of the lateral habenular nucleus, and of these cells, nine units were additionally tested with ACH. Application of the cholinergic transmitter caused enhanced activity in eight of these cells, the remaining unit being inhibited. The responses to melatonin and NOR varied significantly depending on whether the cells were tested during the day or night. It is apparent from these studies that (1) melatonin, noradrenaline and acetylcholine can bring about direct changes in the firing frequency of pineals cells, and (2) pineal cells do not respond to these substances in the same way. Furthermore, since melatonin application had no effect when nerve cells in brain regions surrounding the pineal organ were tested, the results suggest that melatonin, either produced in the pineal or reaching the gland in the general circulation may be capable of directly influencing the cells engaged in its own synthesis.