Biogenic amines in the hypothalamus of rats after diethyldithiocarbamate or AIMAX treatment, an alternative for norepinephrine depletion1

Abstract

The objective of this study was to determine whether AIMAX (a dithiocarbamoylhydrazine derivative) is suitable for determining the effects of norepinephrine (NE) depletion on reproduction in domestic animals. Therefore, the effect of AIMAX (n = 6) on concentrations of biogenic amines in the medial basal hypothalamus (MBH) and anterior hypothalamic area (AHA) of ovariectomized (OVX) rats primed with ovarian steroids was compared to that of diethyldithiocarbamate (DDC; n = 5), a potent dopamine-beta-hydroxylase (DBH) inhibitor, which is chemically similar to AIMAX. Rats that received only ovarian steroids and saline injections served as controls (n = 6). Treatment with DDC resulted in sedation and reduced body temperature. In contrast, rats behaved normally after AIMAX treatment. AI-MAX reduced (P < .05) NE but increased (P < .05) dopamine (DA) concentrations in MBH and AHA compared with controls. Similar changes in NE and DA concentrations were observed in DDC-treated rats. However, elevated epinephrine (EPI) levels were measured in MBH and AHA of only DDC-treated rats. Serum LH concentrations were suppressed (P < .005) in both AIMAX- and DDC-treated rats compared with control animals. Because AIMAX, like DDC, suppressed hypothalamic NE content and LH secretion, AIMAX should be useful in studying effects of NE depletion on gonadotropin secretion in domestic animals.

Central administration of p-hydroxyamphetamine produces a behavioral stimulant effect in rodents: evidence for the involvement of dopaminergic systems

“…For example, MDL100907, a selective 5-HT 2A antagonist, reversed the locomotor stimulant effects of AMPH in rats without having any effect on locomotor activity (Moser et al 1996), and NA uptake inhibitors antagonized the locomotor-stimulant effect of AMPH (Tyler and Tessel 1980). Furthermore, because the DA-β-hydroxylase inhibitor DDC reduced NA levels (Collins 1965;Chang et al 1995;Gaval-Cruz et al 2008), we used nomifensine, fluoxetine, or DDC treatment to determine whether p-OHA-induced hyperlocomotion is due to DA, 5-HT, or NA release. In the present study, p-OHA-induced locomotor activity was inhibited by pretreatments with nomifensine but not by pretreatments with fluoxetine and DDC.…”

“…Thus, to investigate the involvement of presynaptic release of DA, NA, and 5-HT in p-OHA-induced locomotor activity, first, we used the selective serotonin reuptake inhibitor (SSRI) fluoxetine, previously shown to reduce p-OHA-induced HTR (Oyama et al 1989), for the purpose of inhibiting p-OHA uptake into serotonergic nerve terminals. Next, we used the DA-β-hydroxylase inhibitor diethyldithiocarbamate (DDC), which was shown to reduce NA levels (Collins 1965;Chang et al 1995;Gaval-Cruz et al 2008). If increased NA levels from presynaptic noradrenergic nerve terminals are involved in p-OHAinduced locomotor activity, then DDC treatment is expected to reduce hyperlocomotion.…”

Neuroendocrine regulation of reproduction in male domestic animal species: Role of excitatory amino acids

“…Methallibure (synonym = AIMAX) is a derivative of dithiocarbamoylhydrazine and has actions similar to diethyldithiocarbamate, a potent inhibitor of dopamine β-hydroxylase activity. Treatment of rats with AIMAX suppressed norepinephrine synthesis, increased hypothalamic content of dopamine, and suppressed LH secretion (Chang et al, 1995). Similarly, feeding of AIMAX to gilts inhibited LH secretion (Kesner et al, 1987;Chang et al, 1993b).…”

Pituitary-gonadal Relationship in the Catfish Clarias batrachus (L): A Study Correlating Gonadotrophin-II and Sex Steroid Dynamics

“…The drug treatment stimulated dopamine that inhibits, and suppressed noradrenaline and serotonin that stimulate GTH-II secretion. Methallibure shows chemical similarity with diethyldithiocarbamate, a known inhibitor of dopamine-β-hydroxylase (Chang et al, 1995). The ability of the drug to inhibit GTH-II secretion vis-a-vis reproductive activity and the reversibility of the effects make it a suitable agent for population control of prolific breeders or weed fishes in fish farms.…”