The behavior of protein-calorie-malnourished rats on the elevated plus-maze test: An ethopharmacological analysis
Poychohiology
The behavior o f protein-calorie-malnourished rats on the elevated plus-maze test: An ethopharmacological analysis
GABRIELA M. S. MOREIRA 0
MARIELENA DE ARAUJO 0
LUIZ M. DE OLIVEIRA 0
SEBASTIAO S. ALMEIDA 0
0 University oj Sao Paulo , Ribeirao Preto, Sao Paulo , Brazil
In order to study the effects of the protein--calorie malnutrition on the behavior of rats submitted to the elevated plus-maze, an ethopharmacological analysis was used. Litters (dam plus 6 male pups) were fed ad lib (control) or were fed 5091> of the amount of diet consumed by the control group (malnourished) from birth to 49 days of age. From Day 50 on, all rats were fed ad lib. At 70 days of age, the animals were pharmacologically treated (vehicle or diazepam, 1.5 and 3.0 mg/kg) and were placed, 30 min later, in the center of the elevated plus-maze for a 5-min session. During this session, 11 behaviors believed to indicate anxiety or exploration were measured. The results showed that protein--calorie malnutrition results in increased exploration of the open arms of the maze, higher latency offrrst arm entry, and lower closed-arm returns, indicating lower anxiety or higher impulsiveness. In addition, the protein--calorie-malnourished rats were hyporeactive to the anxiolytic effects of diazepam, indicating possible alterations in the GABA-benzodiazepine system as result of the malnutrition procedure.
-
Protein malnutrition early in life results in morpho
logical, neurochemical, and behavioral changes that per
sist even after a long period of nutritional rehabilitation
(Dobbing, 1987; Levitsky & Strupp, 1995; Morgane et al.,
1993; Morgane, Austin-LaFrance, Bronzino, Tonkiss, &
Galler, 1992; Morgane et al., 1978; Strupp & Levitsky,
1995)
.
Recently, it has been shown that protein malnutrition
during the gestational and/or lactational periods changes
the behavior of rats in animal models of anxiety. Lower
anxiety has been shown for malnourished animals sub
mitted to light-dark transition tests
(Brioni & Orsingher,
1988; Santucci, Daud, Almeida, & de Oliveira, 1994)
, el
evated plus-maze tests
(Almeida, de Oliveira, & Graeff,
1991; Almeida et al., 1994; Almeida, Garcia, & de Oli
veira, 1993; Almeida, Tonkiss, & Galler, 1996c)
, and el
evated T-maze tests
(Almeida, Tonkiss, & Galler, 1996b)
.
This altered behavior of malnourished animals in some
models of anxiety has been interpreted as higher impul
siveness of these animals in a naturalistic aversive situa
tion
(Almeida et al., 1994; Almeida et al., 1996c; Santucci
et al., 1994)
. In addition, it has been demonstrated, in a
variety of animal models of anxiety, that protein malnu
trition changes the reactivity of rats to benzodiazepine
(Al
meida, de Oliveira, Bichuette, & Graeff, 1988; Almeida,
de Oliveira, & Graeff, 1990, Almeida et al., 1994; Al
meida, Soares, Bichuette, Graeff, & de Oliveira, 1992;
Brioni, Cordoba, & Orsingher, 1989; Brioni & Orsingher,
1988)
and nonbenzodiazepine anxiolytic drugs
(Almeida
et al., 1990, 1991)
. Changes in the reactivity of malnour
ished animals to these drugs have been interpreted as the
result of neuroanatomical and/or neurochemical changes
produced by early protein malnutrition on central GABA
benzodiazepine and serotonergic neurotransmitter sys
tems
(Almeida, Tonkiss, & Galler, 1996a, for a review)
.
However, the changes in reactivity to anxiolytic drugs in
animal models of anxiety have been restricted to animals
experiencing both pre- and postnatal protein malnutrition.
Considering that one of the most prevalent situations of
malnutrition in human population is protein-calorie mal
nutrition
(de Onis, Monteiro, Akre, & Clugston, 1993)
and that changes in reactivity to anxiolytic drugs can be
of relevance for therapeutic purposes, it would be inter
esting to study this kind of malnutrition. Therefore, the
main aim of this study was to investigate the effects of
protein-calorie malnutrition on the reactivity of rats to a
benzodiazepine anxiolytic drug (diazepam) using the el
evated plus-maze test. In addition to classical measures
taken from this anxiety model (Pellow, Chopin, File, & Bri
ley, 1985), we incorporated elements of an ethological
analysis as described in previous studies
(Almeida et al.,
1994; Almeida et al., 1993; Almeida et al., 1996b; Cole
& Rodgers, 1994; Cruz, Frei, & Graeff, 1994; Rodgers &
Cole, 1993a, 1993b)
.
PROTEIN-CALORIE MALNUTRITIUN AND ANXiETY
METHOD
Subjects
Eighty-four male Wistar rats from the animal colony of the cam
pus of Ribeirao Preto of the University of Sao Paulo were used.
During the lactation period (21 days), each litter was culled to 6
male pups on the day of birth. From that day on, half of the animals
were suckled by mothers maintained on an ad-lib commercial diet
(Purina), and the other half were suckled by mothers receiving 50%
of the amount of the diet consumed by the ad-lib control group.
After weaning, the animals were housed individually; the malnou (...truncated)