Beatriz J. Vasquez

Naloxone enhancement of memory.

Naloxone enhanced retention when systemically administered to male F344 rats after training in a one-trial inhibitory avoidance task. Further, the memory-enhancing ability of naloxone appears to be opiate receptor dependent, because it was antagonized by morphine. Naloxone also improved retention of rats in an active avoidance task, indicating that the effect of naloxone is not task specific. The influence of naloxone on retention was time dependent in both tasks. The results showed that the drug must be present for a considerable period beginning soon after the onset of memory consolidation in order to be effective. For inhibitory avoidance, it was necessary to administer naloxone immediately after training, and because of its short duration of action, again 30 min later. In the active avoidance task, naloxone was effective only when given both immediately before and, as in the inhibitory avoidance task, within 30 min after the eight acquisition trails. These results provide strong evidence that naloxone influences memory and suggest that endogenous opioid systems are involved in memory storage processes.

Post-training amygdaloid lesions impair retention of an inhibitory avoidance response

The study examined the effect of pre- and post-training bilateral amygdaloid lesions on retention of a one-trial inhibitory avoidance response. Groups of rats, including unimplanted controls and implanted controls, were trained and tested for retention at 4, 7 or 12 days following training. The lesions were made at one of several intervals before or after training: 2 days before, immediately after, or 2, 5 or 10 days after. At all retention intervals the retention of implanted controls was poorer than that of unimplanted controls and, in comparison with both control groups, the retention of animals lesioned before training was impaired. Retention was also impaired by the post-training lesions. The degree of impairment varied with the interval between the training and the lesion: lesions made within 2 days following training impaired retention, while lesions made 10 days following training had no impairing effect. These findings suggest that post-training lesions of the amygdala affect retention by impairing time-dependent processes involved in memory storage. With a sufficiently long training-lesion interval (10 days) an intact amygdala is not essential for retention.

Central and peripheral actions of amphetamine on memory storage

These experiments investigated the effects of central (intracerebroventricular) and peripheral (i.p.) posttraining administration of D-amphetamine on rats retention of a one-trial inhibitory avoidance response. While retention was enhanced by i.p. administration (1.0 mg/kg) the central administration (dose range 50-500 microgram) did not affect retention. In rats given peripheral 6-OHDA 24 h prior to training a lower dose (i.p.) of amphetamine (0.25 mg/kg) was most effective in enhancing retention. These findings suggest that the mrmory enhancing effects of D-amphetamine are mediated at least in part through peripheral systems.

3H-dihydromorphine binding in brain regions of young and aged rats

Abstract Opiate receptor-ligand binding was investigated in brains of young and aged female F344 rats. A significant reduction in the density of binding sites for 3H-dihydromorphine was observed in the thalamus and midbrain of aged rats. Evidence of two binding sites was observed in the anterior cortex of young rats, whereas aged rats exhibited only a single site. The occurrence of pituitary tumors in the old female rats did not affect 3H-dihydromorphine binding. The highest density of dihydromorphine binding sites was found in the diencephalon, and the lowest density in the hippocampus. Receptor densities in the anterior cortex, striatum, amygdala, frontal poles and midbrain were intermediate, and few, if any, high affinity binding sites for dihydromorphine were found in the pons-medulla or posterior cortex.

Enkephalins interfere with acquisition of an active avoidance response

Abstract Leu-enkephalin and Met-enkephalin at a dose of 400 μg/kg i.p. significantly impaired acquisition of a one-way active avoidance response. D-Ala-D-Leu-enkephalin also impaired acquisition but at a lower dose (4 μg/kg). D-Ala-Met-enkephalinamide in a wide dose range (0.04–400 μ/kg) did not alter acquisition of the response. A high dose of naloxone (100 mg/kg) blocked the impairing action of Leu-enkephalin. These results are discussed in terms of multiple opiate receptor species.

Attenuation of amphetamine-induced enhancement of learning by adrenal demedullation

These experiments investigated the effect of immediate posttrial administration of peripherally acting DL-4-hydroxyamphetamine on retention of a one-trial inhibitory avoidance response in intact, adrenal medullectomized, sympathectomized, and medullectomized and sympathectomized rats. In intact rats, 0.82 mg/kg of DL-4-OH-amphetamine enhanced retention performance. In rats sympathectomized by peripheral 6-hydroxydopamine, 24 h prior to training, a lower dose of 4-OH-amphetamine (0.21 mg/kg) was most effective in enhancing retention. Adrenal demedullation abolished the memory enhancing effects of DL-4-OH-amphetamine and also D-amphetamine. These findings suggest that the memory enhancing effects of DL-4-OH-amphetamine and D-amphetamine involve adrenal medullary catecholamines.

Psychopharmacological evidence for increase in receptor sensitivity following chronic morphine treatment

The behavioral effects of cholinergic and adrenergic agents on fixed ratio responding (FR5) were examined in control rats and in rats chronically treated with morphine (5 mg/kg/day). Tolerance to the effects of morphine on total responses was observed, but not on rate of responding. Following tolerance development, the directly acting muscarinic agonist, pilocarpine, depressed the behavior of the morphine-treated animals to a significantly greater degree than that of the controls. Similarly, drugs which directly or indirectly stimulate alpha adrenergic and central dopaminergic receptors also affected the behavior of the morphine-treated rats to a significantly greater degree. One interpretation of these findings is that muscarinic cholinergic, alpha adrenergic, and central dopaminergic receptors become supersensitive to their respective neurotransmitters during chronic treatment with morphine. Such a change in receptor sensitivity could constitute a mechanism underlying the development of tolerance to morphine.

Benzodiazepines alter acquisition and retention of an inhibitory avoidance response in mice

These experiments were performed to examine the effects of graded doses of diazepam, flurazepam, or lorazepam given to Swiss-Webster mice either 30 min prior to training or immediately after training in a one-trial inhibitory (passive) avoidance task. A 350 μA footshock was administered following entry into a darkened compartment and retention was tested three days later. Doses of 10.0 mg/kg diazepam and 20.0 mg/kg lorazepam given before training significantly impaired acquisition, while 1.0 mg/kg flurazepam, given immediately after training, produced retrograde amnesia. These results indicate that benzodiazepines affect memory processes and that various drugs of the benzodiazepine family differentially affect acquisition and memory consolidation.

Age dependent changes in retention in rats I

Abstract These experiments examined the retention of newly acquired responses in 70-day-, 1-year-, and 2-year-old (Fischer 344) rats. In the first experiment, the rats were trained in a one-trial inhibitory (passive) avoidance task and retention performance was tested after training-test intervals ranging from 2 hrs to 6 weeks. When tested 2 hrs after training, 2-year-old rats performed significantly better than did 70-day-old rats. However, at longer intervals, the decline in retention performance (i.e., rate of forgetting) varied directly with age. Two-year-old rats exhibited more rapid loss of the avoidance response than did 70-day-old rats. One-year-old rats exhibited intermediate rates of forgetting. A second experiment examined retention performance tested 1, 7, or 21 days after training in a discriminated avoidance task. In this task as well, the rate of decline in retention performance varied directly with age. Thus, these findings suggest that aged Fischer 344 rats forget recently acquired inform...

Alterations in Dihydromorphine Binding in Cerebral Hemispheres of Aged Male Rats

Abstract: Equilibrium binding of [3H]dihydromorphine was assayed in brain regions of young and aged male F344 rats. Young rats had significantly higher receptor densities than old rats in the frontal poles, anterior cortex, and striatum. In the frontal poles, the decline in receptor concentration with age was accompanied by a significant increase in the apparent affinity of dihydromorphine for receptors, which may be compensatory for the decrease in Bmax. This pattern of receptor alterations is different than that previously observed in aged female rats. Therefore, processes which underlie synaptic alterations with age may be different in males and females.