Differential response to gepirone but not to chlordiazepoxide in malnourished rats subjected to learned helplessness

Abstract

The learned helplessness (LH) paradigm is characterized by learning deficits resulting from inescapable events. The aims of the present study were to determine if protein-calorie malnutrition (PCM) alters learning deficits induced by LH and if the neurochemical changes induced by malnutrition alter the reactivity to treatment with GABA-ergic and serotonergic drugs during LH. Well-nourished (W) and PCM Wistar rats (61 days old) were exposed or not to inescapable shocks (IS) and treated with gepirone (GEP, 0.0-7.5 mg/kg, intraperitoneally, N = 128) or chlordiazepoxide (0.0-7.5 mg/kg, intraperitoneally, N = 128) 72 h later, 30 min before the test session (30 trials of escape learning). The results showed that rats exposed to IS had higher escape latency than non-exposed rats (12.6 ± 2.2 vs 4.4 ± 0.8 s) and that malnutrition increased learning impairment produced by LH. GEP increased the escape latency of W animals exposed or non-exposed to IS, but did not affect the response of PCM animals, while chlordiazepoxide reduced the escape deficit of both W and PCM rats. The data suggest that PCM animals were more sensitive to the impairment produced by LH and that PCM led to neurochemical changes in the serotonergic system, resulting in hyporeactivity to the anxiogenic effects of GEP in the LH paradigm.

Early Postnatal Protein-Calorie Malnutrition and Cognition: A Review of Human and Animal Studies

“…A study conducted in our group showed that rats malnourished in early life presented significant alterations in social interaction behaviors in childhood and these behaviors were related to dominance behaviors in adulthood [45]. During lactation phase the litters were fed diet containing 16% protein (well-nourished) or 6% protein (malnourished).…”

Maternal low-protein diet decreases brain-derived neurotrophic factor expression in the brains of the neonatal rat offspring

“…A multitude of animal studies have delved into the effects of prenatal PEM during gestation and postnatal PEM on behavioral abnormalities in the adult progeny [92, 110]. The protein malnourished rat pups subjected to prenatal and postnatal PEM exhibit greater nesting period and passive [5] but lesser locomotor and exploratory behavior [111] during the preadolescent period while exhibiting aggressive and dominance behavior traits in adulthood [112]. Prenatal and postnatal PEM is also associated with deficits in spatial learning and memory in adult rats despite allowing nutritional recovery [113].…”

Effects of acute stress on learning and memory processes of malnourished rats

“…Considering several prior studies, it is plausible that the behavioral changes observed may be due to morphological, biochemical and/or functional alterations in the Central Nervous System (Almeida et al, 1996a;Bedi, 1991;Cintra et al, 1990;Galler et al, 1995;Huang et al, 2003;Lukoyanov & Andrade, 2000;Matos et al, 2011;Morgane et al, 1993;Morgane et al, 2002;Zhang et al, 2010), specifi cally on stress response regulation (Camargo, Nascimento, & Almeida, 2008;Françolin-Silva & Almeida, 2004;Rocinholi et al, 1997), observed in prenatal (Almeida, Tonkiss, & Galler, 1996b;Almeida, Tonkiss, & Galler, 1996c;Morgane et al, 1993) and postnatal malnutrition (Almeida et al, 1991;Camargo & Almeida, 2005;Castro, Tracy, & Rudy, 1989;Fukuda et al, 2002;Fukuda et al, 2007;Valadares et al, 2010).…”