Amnestic effect of cocaine after the termination of its stimulant action.

The effects of cocaine on memory are controversial. Furthermore, the psychostimulant action of cocaine can be a critical issue in the interpretation of its effects on learning/memory models. The effects of a single administration of cocaine on memory were investigated during the presence of its motor stimulating effect or just after its termination. The plus-maze discriminative avoidance task (PM-DAT) was used because it provides simultaneous information about memory, anxiety and motor activity. In Experiment I, mice received saline, 7.5, 10, 15 or 30 mg/kg cocaine 5 min before the training session. In Experiment II, mice were trained 30 min after the injection of saline, 7.5, 10, 15 or 30 mg/kg cocaine. In Experiment III, mice received 30 mg/kg cocaine 30 min pre-training and pre-test. In Experiment IV, mice received 30 mg/kg cocaine immediately post-training. Tests were always conducted 24 h following the training session. Given 5 min before training, cocaine promoted a motor stimulant effect at the highest dose during the training session but did not impair memory. When cocaine was injected 30 min pre-training, the drug did not modify motor activity, but produced marked amnestic effects at all doses tested. This amnesia induced by cocaine given 30 min pre-training was not related to a state-dependent learning because it was not abolished by pre-test administration of the drug. Post-training cocaine administration did not induce memory deficits either. Our results suggest that the post-stimulant phase is the critical moment for cocaine-induced memory deficit in a discriminative task in mice.

Dissociation of the effects of ethanol on memory, anxiety, and motor behavior in mice tested in the plus-maze discriminative avoidance task.

RATIONALE: Several studies have shown the amnestic effects of ethanol (ETOH). However, while memory tasks in rodents can be markedly influenced by anxiety-like behavior and motor function, ETOH induces anxiolysis and different effects on locomotion, depending on the dose. OBJECTIVE: Verify the effects of ETOH in mice tested in the plus-maze discriminative avoidance task (PMDAT) concomitantly evaluating memory, anxiety-like behavior, and motor behavior. METHODS: ETOH acutely or repeatedly treated mice were submitted to the training session in a modified elevated plus-maze with two open and two enclosed arms, aversive stimuli in one of the enclosed arms, and tested 24 h later without aversive stimuli. Learning/memory, locomotion, and anxiety-related behavior were evaluated by aversive arm exploration, number of entries in all the arms and open arms exploration, respectively. RESULTS: Acute ETOH: (1) either increased (1.2-1.8 g/kg) or decreased (3.0 g/kg) locomotion; (2) decreased anxiety levels (1.2-3.0 g/kg); and (3) induced learning deficits (1.2-3.0 g/kg) and memory deficits (0.3-3.0 g/kg). After repeated treatment, sensitization and tolerance to hyperlocomotion and anxiolysis induced by 1.8 g/kg ETOH were observed, respectively, and tolerance to the amnestic effect of 0.6 (but not 1.8) g/kg ETOH occurred. CONCLUSION: Neither the anxiolytic nor the locomotor effects of ETOH seem to be related to its amnestic effect in the PMDAT. Additionally, data give support to the effectiveness of the PMDAT in simultaneously evaluating learning, memory, anxiety-like behavior, and motor activity by different parameters. Possible relationships between the behavioral alterations found are discussed.

Effects of morphine on the plus-maze discriminative avoidance task: role of state-dependent learning.

RATIONALE: The amnesic effects of morphine may be related to its action on nociception, anxiety, or locomotion. This effect is also suggested to be related to state dependency. OBJECTIVES: The aims of this study were to verify the effects of morphine on mice tested in the plus-maze discriminative avoidance task (DAT) that uses light and noise as aversive stimuli and allows the concomitant evaluation of learning, memory, anxiety, and locomotion and also to verify the possible role of state-dependent learning in the effects of morphine. METHODS AND RESULTS: The DAT was conducted in a modified elevated plus-maze. In the training, the aversive stimuli were applied when mice entered in one of the enclosed arms, whereas in the test, no stimuli were applied. The main results showed that (1) pretraining morphine (5-20 mg/kg i.p.) induced retrieval deficits (evaluated by the time spent in the aversive arm in the test) but not acquisition deficits (evaluated by the decrease in aversive arm exploration along the training); (2) pretest morphine (5-10 but not 20 mg/kg) counteracted this deficit; (3) morphine induced hypolocomotion (decreased number of entries in the arms), irrespective of memory alterations; and (4) morphine did not alter anxiety-like behavior (evaluated by the time spent in the open arms) during the training. CONCLUSIONS: Morphine given before training induces retrieval deficits in mice tested in the DAT, and these deficits could be related to morphine-induced state-dependent learning. Neither the memory deficit induced by pretraining morphine nor the reversal of this deficit by pretest morphine seems to be related to anxiety levels or locomotor alterations.

Effects of pre- or post-training paradoxical sleep deprivation on two animal models of learning and memory in mice.

The aim of the present study was to verify the effects of pre- or post-training paradoxical sleep (PS) deprivation in mice tested in the passive and the plus-maze discriminative avoidance tasks. Three-month-old Swiss male mice were placed in narrow platforms in a water tank for 72 h to prevent the occurrence of PS. Control animals were kept in the same room, but in their home cages. Before or after this period, the animals were submitted to the training session of one of the behavioral tasks. The test sessions were performed 3 and 10 days after the training. The animals that were PS-deprived before the training session showed retention deficits in the test sessions performed 3 days later in both tasks (decreased latency to enter the dark chamber of the passive avoidance apparatus or increased percent time spent in the aversive arm of the plus-maze discriminative avoidance apparatus). Animals that were PS deprived after the training session showed no differences from control animals in the test sessions performed 3 days after the training in any of the tasks, but showed passive and discriminative avoidance retention deficits in the test performed 10 days after the training. The results suggest that both pre- and post-training paradoxical sleep deprivation produce memory deficits in mice. However, these effects have different temporal characteristics.