mise à jour du
1 mars 2010
European J. Pharmacol
Influence of clonidine on the acth-induced
behavioral syndrome
Rosanna Poggiol, anna Valerja Vergoni. salvatore Guarini and Alfio Bertolini
institute of Pharmacology, University of Modena,Italy


In male rats, clonidine in a dose range of 1-3000 pg/kg i.p. antagonized the stretching-yawning syndrome induced by the intraventricular injection of ACTH-(1-24) (3 pg/rat) dose-dependently. On the other hand, the effect of clonidine on ACTH-induced penile erections was potentiation at low doses (5 and 10 pg/kg) and inhibition at the highest doses (1000 and 3000 pg/kg), the intermediate doses (50 and 100 pg/kg) being without effect. There was no relationship between these behavioral effects and the effect on arterial blood pressure.
1. Introduction
On the basis of many pharmacological, biochemical and behavioral data concerning such different phenomena as pain sensitivity, memory, some components of sexual behavior, neuronal firing, adenylate cyclase activity, brain acetyicholine turnover, steroidogenic activity, etc., and following the findings that ACTH peptides (ACTH(1-39), -(1-24), -(1-16), etc.) are the sole endogenous substances to share with opiates an affinity for opiate receptors and that ACTH and 8-endorphin are concomitantly released in response to stressful situations, it has been suggested that ACTH peptides are the endogenous antagonists of opiates (for review see Bertolini and Gessa, 1981; De Wied and Jolies, 1982). That is, ACTH peptides and opiate peptides would be part of an integrated neuromodulatory system with opposite effects, in a sort of functional balance, opiates minimizing and ACTH peptides exacerbating the reactions to the environment by opposite modulation of the CNS neuronal circuits concerned.
Clonidine has many links with opiates: the highest levels of its receptors have been found in many of the areas having high densities of opiate receptors as well: clonidine inhibits the firing of these neurons by interacting with inhibitory s2 presynaptic noradrenergic receptors, and opiates similarly cause a marked reduction in the neuronal firing rate interacting with specific opiate receptors, the end effect being the same; clonidine is a potent antinociceptive agent, 2-10 times more effective than morphine. Its withdrawal elicits symptoms similar to those of opiate withdrawal while it suppresses narcotic withdrawal signs in both animals and man (for review see: Lai and Fielding, 1981). Moreover, at least in some conditions (hypertensive animals), its activity seems to involve the release of a f-endorphin-like peptide (Kunos et al., 1981).
We therefore thought it of interest to study the effect of clonidine on some typical components of the behavioral picture induced by the intracerebroventricular injection of ACTH: stretching-yawning syndrome (SYS) and penile erections (for review see Bertolini and Gessa, 1981).
4. Discussion
In the present experiments, clonidine consistently inhibited stretching and yawning from a threshold dose of 5 pg/kg and in a dose-dependent way, the inhibition being almost complete at 50 pg/kg. On the other hand, penile erections were potentiated by low doses of clonidine (5 and 10 pg/kg), this effect shifting gradually however to inhibition which was complete at the highest doses (1000 and 3000 pg/kg). The increase in the number of penile erections observed at the lowest doses of clonidine might have been due to stimula-
tion of parasympathetic tone when sympathetic tone was not yet sufficiently depressed (Scriabine et al., 1968). It has recently been shown that clonidine also suppresses excessive grooming (Gispen and Isaacson, 1981), another component of the ACTH-induced behavioral picture. Together, Gispen's data and ours thus show that practially the whole ACTH behavioral syndrome is antagonized by clonidine as it is by opiates (Bertolini and Gessa, 1981).
The possibility that the inhibitory effect of clonidine may be the consequence of its hypotensive activity must be ruled out because in our experimental conditions (normotensive rats i.p) the effect of clonidine on arterial blood pressure was uneven with hypertension at the highest dose (3000 tg/kg), a dose which completely abolished both SYS and penile erections. Rather, these data seem further support for the idea that an important component of the behavioral syndrome induced by ACTH peptides is the excitatory modulation of central noradrenergic and dopaminergic transmission (Gispen and Isaacson, 1981; Bertolini et al., 1982).
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