Effect of psychotropic drugs on the contents of melatonin, serotonin and N-acetylserotonin in rat pineal gland.

Abstract

Abstract-In the dark phase, the effects of the psychotropic drugs on the contents of melatonin, serotonin (5-HT) and N-acetylserotonin (NAS) in rat pineal gland were examined. The pineal gland was removed at a certain period of time after subcutaneous injection of the drugs. 5-HT, NAS and melatonin contents in the pineal gland were determined by high performance liquid chromatography with fluorometric detection. A dose-dependent decrease was observed for melatonin content in the administration of diazepam (DZP), hydroxyzine (HYZ), chlorprom azine (CPZ) or haloperidol (HPD). When imipramine (IPM) or amitriptyline (APL) was given to rats, pineal 5-HT content was significantly decreased. On the other hand, the administration of IPM or APL caused increases in pineal NAS and melatonin. Furthermore, the administration of phenytoin (PYT) revealed no changes in the content of pineal indoleamines. These results suggest that the psychotropic drugs widely used in clinical applications could cause significant changes in pineal indoleamine content.

The effects of benzodiazepines on basal and isoproterenol‐stimulated N‐acetyltransferase activity by the rat pineal gland, in vivo and in vitro

“…The failure of diazepam given to the intact rat before the onset of darkness to affect the normal nocturnal rise in NAT activity confirms the report of Zatz and Brownstein [1979] but seems at variance with Wakabayashi et al [1989], who reported reduced pineal melatonin content under these conditions without a change in N-acetylserotonin content. This disparity could result from the differences in species (Fischer vs. Wistar), route of drug administration (subcutaneous vs. intraperitoneal), or the effects of the vehicle carrier (ethanolpropylene glycol in this study).…”

Chronic diazepam administration differentially affects melatonin synthesis in rat pineal and Harderian glands

“…We report herein, that 21 days administration of diazepam decreased pineal melatonin levels and altered pineal NAT activity, without affecting the activity of HIOMT. We show that diazepam administration on a long-term basis resulted in an inhibition of NAT activity and a decrease of pineal melatonin concentrations to the same magnitude as that observed with acute diazepam administration (Wakabayashi et al 1989(Wakabayashi et al , 1991a(Wakabayashi et al , 1991b. Therefore, a chronic treatment with diazepam compared to an acute administration did not affect differently pineal melatonin synthesis, which strongly suggests that diazepam affects pineal melatonin synthesis, at least in the rat, at the beginning of the treatment.…”

“…Indeed, it has been shown that a single subcutaneous injection of diazepam at a dose of 3 mg/kg body weight, 1 h before dark onset, suppressed nocturnal elevation of N-acetylserotonin (NAS) and melatonin content and delayed the time at which the pineal melatonin content reaches a maximum by 2 h in the dark phase. It also caused a remarkable inhibition of NAT activity and failed to produce any significant changes in the content of pineal serotonin and HIOMT activity 5 h after treatment (Wakabayashi et al 1989(Wakabayashi et al , 1991a.…”

“…Melatonin is the major secretory product of the pineal gland (Reiter 1991) and displays benzodiazepine-like pharmacological properties (Philo and Berkowitz 1984;Lewis et al 1990). Several investigations have been undertaken to elucidate the relationship between melatonin and diazepam (Zatz and Brownstein 1979;Matthew et al 1984;Lowenstein et al 1985;Morton 1986;Oxenkrug and Harris 1988;Monteleone et al 1989;Wakabayashi et al 1989Wakabayashi et al , 1991aWakabayashi et al , 1991bOxenkrug and Requintina 1990;Winters et al 1991;Atsmon et al 1996). Benzodiazepine receptors are divided into high affinity (nM) "central" and lower (µM) affinity "peripheral" receptors (Iversen 1978;Surany-Cadotte et al 1987).…”

“…The rat pineal gland is considered to have peripheral-type receptors (Mattew et al 1984;Lowenstein et al 1985), while bovine and human pineal glands are thought to have both peripheral and central types (Lowenstein et al 1984;Surany-Cadotte et al 1987). Several in vivo studies in humans and rodents suggest that administration of diazepam alters pineal function, and consequently melatonin biosynthesis (Zatz and Brownstein 1979;Morton 1986;Oxenkrug and Harris 1988;Monteleone et al 1989;Wakabayashi et al 1989Wakabayashi et al , 1991aWakabayashi et al , 1991bOxenkrug and Requintina 1990;Winters et al 1991). All of these reports, however, studied the acute effects of diazepam and we could not find in the literature studies on the chronic effects of diazepam.…”