Antinociception induced by acute oral administration of sweet substance in young
and adult rodents: The role of endogenous opioid peptides chemical mediators and
Renato Leonardo de Freitasa,b, João Marcus Lopes Küblera,
Daoud Hibraim Elias-Filhoa,b, Norberto Cysne Coimbraa,b,⁎
aLaboratório de Neuroanatomia & Neuropsicobiologia, Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (USP), Av. dos Bandeirantes,
3900, 14049-900, Ribeirão Preto (SP), Brazil
bInstituto de Neurociências e Comportamento, Campus Universitarius da Universidade de São Paulo (USP) em Ribeirão Preto, Av. dos Bandeirantes, 3900, Ribeirão Preto (SP),
a b s t r a c ta r t i c l e i n f o
Received 8 June 2011
Received in revised form 23 November 2011
Accepted 10 December 2011
Available online 16 December 2011
Sweet substance-induced antinociception
Endogenous opioid peptides
The present work aimed to investigate the effects of acute sucrose treatment on the perception of painful
stimuli. Specifically, we sought to determine the involvement of the endogenous opioid peptide-mediated
system as well as the role of the μ1-opioid receptor in antinociception organisation induced by acute sucrose
intake. Nociception was assessed with the tail-flick test in rats (75, 150 and 250 g) of different ages acutely
pre-treated with 500 μL of a sucrose solution (25, 50, 150 and 250 g/L) or tap water. Young and Adult rats
(250 g) showed antinociception after treatment with 50 g/L (during 5 min) and 150 g/L and 250 g/L (during
20 min) sucrose solutions. Surprisingly, this antinociception was more consistent in mature adult rodents
than in pups. To evaluate the role of opioid systems, mature adult rodents were pre-treated with different
doses (0.25, 1 or 4mg/kg) of the non-selective opioid receptor antagonist naloxone, the selective μ1-opioid
receptor antagonist naloxonazine or vehicle followed by 250 g/L sucrose solution treatment. Sucrose-
induced antinociception was reduced by pre-treatment with both naloxone and naloxonazine. The present
findings suggest that sweet substance-induced hypo-analgesia is augmented by increasing sucrose concentra-
tions in young and adult rodents. Acute oral sucrose treatment inhibits pain in laboratory animal by mediating
endogenous opioid peptide and μ1-opioid receptor actions.
© 2011 Elsevier Inc.
There is evidence that the consumption of sweet palatable sub-
stances produces analgesia in animals (Holder, 1988; Blass and Shide,
1994; Segato et al., 1997; Irusta et al., 2001; Anseloni et al., 2002).
Furthermore, concentrated sucrose solutions seem to reduce crying
and other pain-related behaviours in healthy human infants and su-
in full-term infants (Haouari et al., 1995; Abad et al., 1996).
There is evidence for antinociception and c-fos immunoreactivity
in endogenous opioid- and monoamine-containing cell groups of
the mesencephalon and pons after an intraoral sucrose infusion in
infant rats (Anseloni et al., 2002). It has been demonstrated that
sweet substances may also increase the analgesic properties of
opiates (Lieblich et al., 1983; Marks-Kaufman et al., 1988; Roane
and Martin, 1990; Kanarek et al., 1991), and morphine produces
dose-dependent increases in antinociception elicited by palatable
substances (Kanarek et al., 2000). In fact, palatable substances, such
as sucrose and saccharin, may interact with the opioid system, mod-
ifying its sensitivity (Davis et al., 1956; Lieblich et al., 1983; Bergmann
et al., 1985; Blass and Fitzgerald, 1988; Klein and Green, 1988; Marks-
Kaufman et al., 1988; Roane and Martin, 1990; Rebouças et al., 2005).
The bi-directional relation between endogenous opioids and inges-
tion of sweet substances has motivated research examining a possible
link between intake of sweet substances and antinociception. The
consumption of sweet food has been shown to modulate μ- and κ-
opioid receptors (Kanarek et al., 1997a,b). Some publications have
reported that orogustatory and orotactile analgesia are absent or mini-
malatpostnatalday0 (P0) and appearconsistentlyfromP3toP10–P17
(Anseloni et al., 2002, 2004). However, other studies found sweetened
substances caused persistent opioid and non-opioid analgesia in adult
rats (Segato et al., 1997; Irusta et al., 2001; Miyase et al., 2005;
has not been consistently demonstrated in adult humans.
Pharmacology, Biochemistry and Behavior 101 (2012) 265–270
⁎ Corresponding author at: Laboratório de Neuroanatomia & Neuropsicobiologia,
Departamento deFarmacologia,Faculdade deMedicinadeRibeirãoPreto daUniversidade
de São Paulo (USP), Av. dos Bandeirantes, 3900, 14049-900, Ribeirão Preto (SP), Brazil.
Tel.: +55 16 3602 3116; fax: +55 16 3602 3349.
E-mail address: email@example.com (N.C. Coimbra).
0091-3057 © 2011 Elsevier Inc.
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