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).
-Poggioli
R, Valerja Vergoni A, et al. Influence of
clonidine on the ACTH-induced behavioral
syndrome, European J. Pharmacol.
1984;101:299-301
-Poggioli R
et al Nitric oxide is involved in the
ACTH-induced behavioral syndrome Peptides
1995;16(7)1263-1268
