Behavioural Brain Research 153 (2004) 537–541
Research report
Evidence that the effect of melanocortins on female sexual
behavior in preoptic area is mediated by the MC3 receptor
Participation of nitric oxide
Carla Nocetto
a
, Andrea B. Cragnolini
a
, Helgi B. Schiöth
b
, Teresa N. Scimonelli
a,∗
a
Departamento de Farmacolog´ ıa, Facultad de Ciencias Qu´ ımicas, Haya de la Torre y Medina Allende,
Ciudad Universitaria, Universidad Nacional de Córdoba, 5000 Córdoba, Argentina
b
Department of Neuroscience, Section of Pharmacology, Uppsala University, Uppsala, Sweden
Received 7 August 2003; received in revised form 9 December 2003; accepted 11 January 2004
Available online 12 February 2004
Abstract
-MSH is involved in reproductive processes and can regulate the expression of lordosis, an important component of female reproductive
behavior in rats and many other species. In this study, we investigated the effects of MSH peptides on lordosis behavior when injected in
medial preoptic area (POA) of ovariectomised rats primed with estradiol. The results show an increase in lordotic activity after bilateral
administration of -MSH and -MSH. Interestingly, the treatment with the MC4 receptor antagonist HS014 did not block the stimulatory
effect of -MSH. Moreover, the injection of HS014 did not itself modify the lordosis quotient.
Nitric oxide has been suggested to play a crucial role in the regulation of lordosis behavior via stimulation of guanylyl cyclase to
synthesize cGMP. In order to determine the participation of NO in the effect of the melanocortins, another group of rats were treated with
l-NAME, an inhibitor of NOS, alone or 15 min before the injection of -MSH or -MSH. The injection of l-NAME into the POA of
E-primed rats 15 min before the test for sexual receptivity did not modify significantly the lordosis quotient at the two doses examined.
The treatment with l-NAME at the lowest dose completely abolished the stimulatory effect of -MSH and -MSH on sexual behavior.
The results indicate that the effects of MSH peptides on female sexual behavior in this area are mediated through specific MC receptor,
that could be the MC3 receptor and that NO mediates the melanocortins effects.
© 2004 Elsevier B.V. All rights reserved.
Keywords: Lordosis; Melanocortin receptors; Preoptic area; Nitric oxide
1. Introduction
Hormonal regulation of reproduction involves changes in
the activity of the neural circuits governing LH release and
lordosis behavior. Therefore, the ovarian steroids action in
the brain ensures reproductive success by maximizing the
probability that a female will contact and be inseminated
by a male at the optimal time for achieving fertilization.
Both neurons of the hypothalamus and POA participate in
the neuroendocrine integration of lordosis behavior and the
preovulatory LH surge [4].
Gonadal steroids acting at the level of the central nervous
system controlled mammalian sexual behavior. Besides, the
multitude of transmitters that affect reproductive behavior
∗
Corresponding author. Tel.: +54-351-4334437;
fax: +54-351-4334420.
E-mail address: tscimonelli@mail.fcq.unc.edu.ar (T.N. Scimonelli).
indicate that a variety of neuronal systems must be involved
in controlling various aspects of sexual activity. Neuropep-
tides are involved in reproductive processes, possibly act-
ing to enhance the action of gonadal steroids. Thus, -MSH
can stimulate female receptivity and has been investigated
in greater depth than other POMC peptides in relation to fe-
male sexual behavior. The stimulatory effect of -MSH can
be seen after administration into the third ventricle, median
eminence, POA and VMN, where it is as potent as GnRH
[6,7,9,21]. Although -MSH alters DA activity specifically
and selectively in the VMN, the latter does not mediate its
effect since a DA antagonist does not inhibit -MSH ac-
tivity. The stimulatory action of -MSH may, however, be
mediated by NA, since a -adrenergic antagonist can block
the stimulatory effect of -MSH, and -MSH can stimulate
the release of NA from hypothalamic fragments in vitro [6].
Interestingly, -MSH also causes significant increase in lor-
dosis behavior in female rats after injections into the ventro-
0166-4328/$ – see front matter © 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.bbr.2004.01.014