Caffeine/nutrition interaction in the rat brain: Influence on latent inhibition and cortical spreading depression

Abstract

Caffeine, like malnutrition, can produce behavioral and electrophysiological alterations. However, the interaction of both factors remains unclear. Here this interaction has been studied in male Wistar rats previously malnourished during the lactation period by feeding their dams the "regional basic diet" of Northeast Brazil, containing about 8% protein, predominantly from vegetable sources (RBD(8)). At 70-75days of life, a subset of the pups was treated intraperitoneally with 30mg/kg caffeine for 4days while being tested according to the behavioral model of latent inhibition. Another group was subjected to an electrophysiological recording of the phenomenon known as cortical spreading depression, and the effects of caffeine injected during the recording session were evaluated. Caffeine did not affect cortical spreading depression, but antagonized latent inhibition in both the RBD(8)-malnourished rats and in the well-nourished control group fed a chow diet with 22% protein. This effect of caffeine was not seen in malnourished rats fed a protein-supplemented RBD (protein increased to 22% by increasing the proportion of foodstuffs from vegetable origin; RBD(22) group), suggesting that the amino acid imbalance of this diet may modulate the caffeine effects on latent inhibition. The results indicate a differential effect of caffeine in the latent inhibition behavioral model, as compared to the cortical spreading depression phenomenon, and this effect is influenced by the early nutritional status of the animal. We suggest that caffeine may modulate dopaminergic subcortical receptors participating in attention processes, but does not interact at the cortical level, in a way that would affect cortical spreading depression.

Zinc treatment ameliorates diarrhea and intestinal inflammation in undernourished rats

“…Although the RBD, enriched in carbohydrate and with low protein, has been used in several studies to induce malnutrition [27,28], our study is the first to evaluate a dual hit of RBD-induced malnutrition and osmotic diarrhea, along with the role of zinc as a gut-trophic nutrient to improve intestinal inflammation, intestinal bacterial translocation, and intestinal morphology.…”

Deletion of striatal adenosine A2A receptor spares latent inhibition and prepulse inhibition but impairs active avoidance learning

“…These seemingly conflicting outcomes might be attributable to differences in dosage (namely, 10 vs. 30 mg/kg) and/or learning paradigm chosen (i.e., conditioned taste aversion vs. condition active avoidance) to measure LI. However, interpretation of De Aguiar et al’s study [48] should be cautioned, because conditioned taste aversion was strongly reduced in the caffeine-treated animals regardless of stimulus pre-exposure condition. In the absence of clear learning in the nPE condition, one essentially cannot assess the impact of stimulus pre-exposure, and any conclusion on LI is not warranted [see Figure 3 of 48].…”

“…However, interpretation of De Aguiar et al’s study [48] should be cautioned, because conditioned taste aversion was strongly reduced in the caffeine-treated animals regardless of stimulus pre-exposure condition. In the absence of clear learning in the nPE condition, one essentially cannot assess the impact of stimulus pre-exposure, and any conclusion on LI is not warranted [see Figure 3 of 48]. Our data showed that LI was not impaired in st-A 2A R-KO mice – neither in the CTA nor the active avoidance paradigm.…”

“…Available data are limited to two studies testing the effect of the mixed A 1 R/A 2A R antagonist caffeine, which yielded conflicting outcomes. De Aguiar et al [48] recently reported that 30 mg/kg caffeine impaired LI of conditioned taste aversion. Based on the antagonistic A 2A R-D 2 R interaction in the striatum, the authors speculated that caffeine disrupted LI by blocking striatal A 2A R thereby leading to a potentiation/disinhibition of D 2 R-mediated transmission, which is known to attenuate LI [34].…”

“…Based on the antagonistic A 2A R-D 2 R interaction in the striatum, the authors speculated that caffeine disrupted LI by blocking striatal A 2A R thereby leading to a potentiation/disinhibition of D 2 R-mediated transmission, which is known to attenuate LI [34]. A separate shuttle-box active avoidance study, however, reported that LI remained intact up to a dose of 10mg/kg caffeine [48]. These seemingly conflicting outcomes might be attributable to differences in dosage (namely, 10 vs. 30 mg/kg) and/or learning paradigm chosen (i.e., conditioned taste aversion vs. condition active avoidance) to measure LI.…”