Chronic caffeine consumption prevents cognitive decline from young to middle age in rats, and is associated with increased length, branching, and spine density of basal dendrites in CA1 hippocampal neurons.

Chronic caffeine consumption has been inversely associated with the risk of developing dementia and Alzheimer's disease. Here we assessed whether chronic caffeine treatment prevents the behavioral and cognitive decline that male Wistar rats experience from young (≈3 months) to middle age (≈10 months). When animals were young they were evaluated at weekly intervals in three tests: motor activity habituation in the open field (30-min sessions at the same time on consecutive days), continuous spontaneous alternation in the Y-maze (8 min), and elevated plus-maze (5 min). Afterward, rats from the same litter were randomly assigned either to a caffeine-treated group (n=13) or a control group (n=11), which received only tap water. Caffeine treatment (5 mg/kg/day) began when animals were ≈4 months old, and lasted for 6 months. Behavioral tests were repeated from day 14 to day 28 after caffeine withdrawal, a time period that is far in excess for the full excretion of a caffeine dose in this species. Thirty days after caffeine discontinuation brains were processed for Golgi-Cox staining. Compared with controls, we found that middle-aged rats that had chronically consumed low doses of caffeine (1) maintained their locomotor habituation during the second consecutive day exposure to the open field (an index of non-associative learning), (2) maintained their exploratory drive to complete the conventional minimum of nine arm visits required to calculate the alternation performance in the Y-maze in a greater proportion, (3) maintained their alternation percentage above chance level (an index of working memory), and (4) did not increase the anxiety indexes assessed by measuring the time spent in the open arms of the elevated plus maze. In addition, morphometric analysis of hippocampal neurons revealed that dendritic branching (90-140 µm from the soma), length of 4th and 5th order branches, total dendritic length, and spine density in distal dendritic branches were greater in the basal but not the apical dendrites of CA1 pyramidal neurons from rats chronically treated with caffeine, in comparison with their age- and littermate-matched controls. Altogether, the present findings strengthen the epidemiological observations suggesting that prolonged caffeine intake prevents the cognitive decline associated with aging, and open the possibility that this process could be mediated by promoting the growth of dendrites and spines in neurons of the adult mammalian brain.

Improvement of postural adjustment steps in hemiparkinsonian rats chronically treated with caffeine is mediated by concurrent blockade of A1 and A2A adenosine receptors.

Chronic treatment with the non-selective adenosine receptor antagonist caffeine produces full recovery of the contralateral adjusting steps in hemiparkinsonian rats. In order to disclose which adenosine receptor subtype mediates this effect, a group of hemiparkinsonian rats (n=9) was treated with caffeine (5.15 mumol/kg/day), or equimolar doses of selective A1 (DPCPX) or A2A (ZM 241385) adenosine receptor antagonists, administered in a counterbalanced order over periods of 3 weeks, interspersed with equivalent washout intervals. Treatment with ZM 241385 caused full recovery (102+/-6%) of the contralateral forepaw stepping, while the maximal effect of DPCPX was only 73+/-7% of that produced by caffeine. The maximal effect of caffeine and ZM 241385 remained stable throughout the treatment period. The response to DPCPX showed more fluctuations, but tolerance did not develop. Stepping improvement was significantly faster with DPCPX than with ZM 241385, while caffeine had intermediate values. Stepping decrease after treatment interruption was faster with ZM 241385 than with caffeine, while DPCPX had intermediate values. In other experiments with the same rats, addition of the A2AR agonist CGS 21680 (5.15 mumol/kg) or the A1R agonist CCPA (2.71 mumol/kg) during the second week of caffeine treatment reversed the improvement of contralateral stepping by 59+/-4% and 30+/-3%, respectively. The combined treatment with CGS 21680 and CCPA caused complete reversal of the contralateral stepping recovery afforded by caffeine, which was more than additive (114+/-5%) compared with the sum of the maximal inhibition produced by either agonist administered alone (89+/-4%). In all cases, after interrupting the adenosine agonists, the effect of caffeine was fully restored. None of the aforementioned treatments induced significant changes in the stepping of the ipsilateral forepaw. Collectively, these results suggest that the improvement of postural adjustments induced by chronic treatment with low doses of caffeine in hemiparkinsonian rats is mediated by concurrent blockade of A1 and A2A adenosine receptors, with a larger involvement of the latter.

A novel rotometer based on a RISC microcontroller.

A new, low-cost rotometer, based on a reduced instruction set computer (RISC) microcontroller, is presented. Like earlier devices, it counts the number and direction of full turns for predetermined time periods during the evaluation of turning behavior induced by drug administration in rats. The present stand-alone system includes a nonvolatile memory for long-term data storage and a serial port for data transmission. It also contains a display for monitoring the experiments and has battery backup to avoid interruptions owing to power failures. A high correlation was found (r > .988, p < 2 x 10(-14)) between the counts of the rotometer and those of two trained observers. The system reflects quantitative differences in turning behavior owing to pharmacological manipulations. It provides the most common counting parameters and is inexpensive, flexible, highly reliable, and completely portable (weight including batteries, 159 g).