Sex-dependent effects of neonatally administered morphiceptin and D-ala-D-leu-enkephalin on maze learning in rats

Newborn rats were injected (ip) with morphiceptin [72.7 micrograms/kg (a mu-type opioid receptor agonist)], D-alanine2-D-leucine5-enkephalin [79.4 micrograms/kg (a delta-receptor agonist)], or saline for 7 days after birth. Testing on a complex maze on Day 25 revealed a significant sex-dependent facilitation of performance by the opioid peptides. Peptide-treated females performed better than the males on the first day of training as measured by errors. Opioid treatment increased mortality, as three times as many peptide-treated animals died in comparison to the saline control group. Peptide treatment did not affect locomotor activity measured in an open field. Weight at Day 24 was also affected by the peptide treatment, females and males injected with the opioids being lighter and heavier, respectively, than the control group.     

Calcium channel antagonists enhance retention of passive avoidance and maze learning in mice

Although a number of studies have shown that treatment with calcium channel antagonists (CCAs) can ameliorate impairments in learning and memory in aged animals, evidence for a general nootropic effect of CCAs in neurologically normal young adult animals is ambiguous. This study attempts to resolve some of this ambiguity by comparing the effects of several CCAs on retention of passive avoidance learning and acquisition and retention of appetitively motivated spatial discrimination learning in young adult mice. Animals were trained in a step through passive avoidance apparatus and, immediately after training, injected subcutaneously with different doses of nimodipine, nifedipine, amlodipine, flunarazine, diltiazem, or verapamil. Retention was tested 24 h after training. In the maze-learning task mice were treated with the same doses of the aforementioned CCAs immediately after a brief training session in a linear maze and retention was tested 24 h after training. The most effective dose of each agent in the maze-retention experiment was administered to additional groups of animals 1 h prior to training to determine the effects of CCAs on acquisition processes. The effects of central administration of CCAs were examined by intracerebroventricular injection of different doses of amlodipine immediately after passive avoidance training. Results showed (1) all peripherally administered drugs except verapamil facilitated retention of passive avoidance training in a dose-dependent manner, (2) all drugs dose dependently facilitated retention of linear maze learning, (3) all doses of the drugs (except verapamil) which facilitated maze retention also facilitated maze learning, and (4) central administration of the dihydropyridine amlodipine produced a dose-dependent facilitation of the retention of passive avoidance learning. These data indicate that drugs which block calcium channels can enhance retention of two different types of learning in mice.     

The effects of binge MDMA on acquisition and reversal learning in a radial-arm maze task

The current study used the partially-baited radial-arm maze paradigm to study the effects of a single-treatment high-dose exposure ('binge') to MDMA (± 3,4-methylenedioxymethaphemtamine or 'Ecstasy') on memory task acquisition. Sprague-Dawley rats were administered a binge dose (4 × 10 mg/kg) of MDMA and their ability to subsequently acquire the radial-arm maze task was compared against saline controls. The MDMA-treated rats were significantly slower to learn the task and made more reference memory errors than the controls. Working memory function was found to be relatively unimpaired. Following a reversal of task rules the MDMA-treated rats were again significantly slower to acquire the appropriate rule despite having eventually achieved a similar level of overall performance as control rats. However evidence of drug tolerance was found when all rats were challenged with an acute low dose of MDMA (1 × 4.0 mg/kg) because the binge MDMA rats were relatively less impaired. Therefore, although binge treated MDMA rats were able to achieve very accurate performance equivalent to the controls they took significantly longer to do this and were less able to adapt their behavior to a change in task rules. In addition the binge treated MDMA rats displayed tolerance to acute MDMA exposure. These findings are consistent with the possibility that human Ecstasy users may show deficits in acquiring information and may experience deficits in cognitive flexibility as well as developing tolerance to the drug with repeated exposure.     

Chronic nicotine and withdrawal effects on radial-arm maze performance in rats

Rats were tested for choice accuracy in an eight-arm radial maze during and after chronic administration of nicotine via subcutaneously implanted glass and Silastic capsules. Nicotine administration significantly improved choice accuracy relative to controls. The effect gradually became apparent over the first 2 weeks of exposure and persisted through the third week. Surprisingly, the significant facilitation of the nicotine-treated rats relative to controls continued for 2 weeks after the end of nicotine administration. No effects of nicotine were seen on choice latency or the strategy to make adjacent arm entries.     

Perceptual learning in maze discriminations

In Experiment 1, rats were trained on a discrimination between rubber- and sandpaper-covered arms of a maze after one group had been pre-exposed to these intra-maze cues. Pre-exposure facilitated subsequent discrimination learning, unless the discrimination was made easier by adding further discriminative stimuli, when it now significantly retarded learning. In Experiment 2, rats were trained on an extra-maze spatial discrimination, again after one group, but not another, had been pre-exposed to the extra-maze landmarks. Here too, pre-exposure facilitated subsequent discrimination learning, unless the discrimination was made substantially easier by arranging that the two arms between which rats had to choose were always separated by 135°. The results of both experiments can be explained by supposing that perceptual learning depends on the presence of features common to S+ and S-.