Biomedical subjects

A L Markowska

Publications and source records attributed to A L Markowska.

31 records · Page 2Linked to original sources

PubMed1993

3,4-Methylenedioxymethamphetamine, serotonin and memory.

The recreational drug (+/-)-3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") is toxic to central serotonin (5-HT) neurons, but few long-term functional consequences of MDMA neurotoxicity have been identified. Because 5-HT has been implicated in learning and memory, the present study was undertaken to examine whether MDMA, by damaging 5-HT neurons, altered mnemonic function on a long-term basis. Rats were treated with saline, MDMA or 5,7-dihydroxytryptamine/desmethylimipramine. The latter treatment group was included to assess the effects of larger 5-HT neuronal lesions than are possible with MDMA. Four weeks after drug treatment, memory was assessed in three different variations of spatial alternation in a T-maze: acquisition with a constant and short delay interval, performance with variable delays and treatment with scopolamine. Upon completion of the behavioral studies, the neurotoxic effects of the drugs were assessed chemically and anatomically. MDMA, which produced a substantial and selective reduction of brain 5-HT, had no effect on choice accuracy. 5,7-dihydroxytryptamine/desmethylimipramine which produced a near-total reduction of 5-HT and a modest reduction of norepinephrine, impaired choice accuracy in all three variations of the task. These data suggest that selective damage to the 5-HT system, like that produced by MDMA, is not sufficient to impair memory, but that combined damage to the 5-HT and norepinephrine systems can disrupt performance in tasks that require recent memory. Because Alzheimer's disease involves impairments in acetylcholine, 5-HT and norepinephrine systems, animals with combined lesions may provide a useful model to study the mnemonic dysfunctions characteristic of this disease.

3,4-Methylenedioxyamphetamine↗

PubMed1991

Serotonin influences the behavioral recovery of rats following nucleus basalis lesions.

The present study investigated the effects of serotonergic depletion upon the performance of rats with lesions of the nucleus basalis magnocellularis (NBM) in a nonspatial memory task. NBM lesions were made by injections of ibotenic acid. Serotonin was depleted by systemic injections of p-chloroamphetamine (PCA). After four weeks of testing, the choice accuracy of PCA rats was not different from that of control rats (CON), while the choice accuracy of NBM rats and rats with combined treatment (NBM + PCA) was significantly lower than CON rats, but not different from each other. After prolonged testing, performance improved in NBM rats, but not in NBM + PCA rats indicating that simultaneous loss of both cholinergic and serotonergic neurotransmission produced a significantly longer lasting behavioral deficit than the loss of cholinergic neurotransmission alone.

Animals↗

PubMed1990

Nucleus basalis magnocellularis and memory: differential effects of two neurotoxins.

Although the cholinergic system is involved in memory, noncholinergic systems may also contribute to memory. Lesions of the nucleus basalis magnocellularis (NBM) produce behavioral impairments and reduction of cholinergic markers in the frontal cortex (FC). The present study compared the behavioral effects of lesions made with two different neurotoxins, ibotenic (IBO) acid and quisqualic (QUIS) acid. IBO or QUIS was injected into the NBM, and rats were tested in three different tasks: cued delayed nonmatch-to-sample (CDNMS), spatial delayed nonmatch-to-sample (SDNMS), and spatial two-choice simultaneous discrimination (STCSD). IBO producted a greater behavioral impairment than QUIS in the CDNMS and the SDNMS, although QUIS produced a greater drop in choline acetyltransferase (ChAT) activity in the cortex than IBO. At the end of behavioral testing, IBO rats, but not QUIS rats, were impaired in the retention of both tasks. The fact that QUIS lesions produced a greater loss of NBM cholinergic neurons, as determined by decreased ChAT activity, but less of a behavioral impairment in both a spatial and nonspatial task, suggests that the loss of noncholinergic NBM neurons must contribute to the memory impairments following NBM cell loss.

Animals↗

PubMed1990

Dietary acetyl-L-carnitine improves spatial behaviour of old rats.

Acetyl-L-carnitine was given to aging rats to determine the extent to which it changed age-related impairments in several different behaviours. One group of rats was given acetyl-L-carnitine, 80 mg/day, beginning at 16 months of age. A second group of rats was housed and treated identically, except that no drug was administered. At 22 months of age, both groups of rats began a series of behavioural tests, along with a group of young rats, four months of age. The tests included: place learning on a circular platform, probe reversal of place learning on a circular platform, two choice simultaneous spatial discrimination in the stem of a T-maze spatial alternation in the arms of a T-maze, and sensory-motor behaviour (initiation of walking, turning in an alley, walking on a square, round, and rectangular bridge, turning on an inclined grid, holding on to a wire, light-dark preference). The tasks varied in their sensitivity to age-related impairments. These data indicate that long-term therapy with acetyl-L-carnitine attenuates certain age-related cognitive deficits and may have a beneficial effect on longevity.

Acetylcarnitine↗

PubMed1989

A comparative analysis of the role of fornix and cingulate cortex in memory: rats.

In order to compare the role of the fornix (FX) and cingulate cortex (CC) in memory, rats were trained in a series of discriminations using procedures that were the same as those used for monkeys (Murray et al. 1986, 1988). A spatial delayed nonmatching-to-sample (DNMS) discrimination tested recent memory for spatial location in a T maze using interrun intervals (IRI) that varied from 5 s to 15 min. FX and CC lesions produced a substantial impairment in the performance of this task during postoperative testing. Three conditional discriminations (CD) followed. In each one, the rat was presented with two objects, only one of which was correct. The nature of the conditional stimuli changed in each discrimination: the place of the maze in the room; the direction that the rat moved to approach the objects; the side (left or right) to which the rat turned. Control rats learned all three types of conditional discriminations. FX and CC lesions did not impair choice accuracy. In a subsequent repetition of the spatial DNMS procedure, FX and CC lesions again produced a substantial impairment, indicating that the lack of an impairment in the three CDs was not due to recovery of function. These data indicate that the hippocampal system and its connections through the fornix are importantly involved in spatial working memory in both rats and monkeys, and that the CDs do not require this type of memory. The results are discussed in the context of different theories of the brain mechanisms involved in memory.

Animals↗

PubMed1989

Basal forebrain lesions and memory: alterations in neurotensin, not acetylcholine, may cause amnesia.

Behavioral impairments produced by lesions of the nucleus basalis magnocellularis (NBM) are usually attributed to the loss of cholinergic cells. A comparison between the effects of 2 different neurotoxins, ibotenic (IBO) and quisqualic (QUIS) acid, reveals that this interpretation is inconsistent with the data. Rats were given injections of either IBO or QUIS into the NBM and tested on an alternation task in a T-maze. At the start of behavioral testing, both IBO and QUIS rats had impaired choice accuracy. At the end of behavioral testing, however, IBO rats, but not QUIS rats, were more impaired than controls, and IBO rats were more impaired than QUIS rats. IBO decreased choline acetyltransferase (ChAT) activity and [3H] neurotensin binding in the neocortex. QUIS decreased ChAT activity but did not change [3H] neurotensin binding. The cholinergic system may not be the critical component responsible for behavioral impairments following NBM lesions.

Acetylcholine↗

PubMedDate not supplied

Acetyl-1-carnitine. 1: Effects on mortality, pathology and sensory-motor performance in aging rats.

Three different test sites assessed the effects of acetyl-1-carnitine (AC) on age-related changes in general health, sensory-motor skills, learning, and memory. Two groups of rats began the experiments at 16 months of age. One group (OLD-AC) was given AC, 75 mg/kg/day, beginning at 16 months. The other group (OLD-CON) was treated identically except it was not given the drug. Beginning at 22 months of age, these rats and a group of young (3-4 months old) rats (YG-CON) were given a series of sensory-motor tasks. AC decreased mortality, and had no reliable effect on body weight, fluid intake, or the general health of the rats. These data indicate that a chronic dose of AC does not interfere with food and water intake, and may increase longevity. An age-related decline of performance occurred in most of the sensory-motor tasks; locomotor activity was reduced in a novel environment and in a runwheel, and the ability to prevent falling was reduced in tests on a taut wire, rotorod, inclined screen, and several types of elevated bridges. An age-related decline of performance did not occur in grooming, or in the latency to initiate several different behaviors. AC had no effect on performance in any sensory-motor task. These data indicate that the improvements produced by AC in some tests of spatial memory may be due to the effects of AC on cognitive abilities rather than on sensory-motor skills.

Acetylcarnitine↗

PubMedDate not supplied

Acetyl-1-carnitine. 2: Effects on learning and memory performance of aged rats in simple and complex mazes.

Acetyl-1-carnitine (AC) was administered via drinking water for six months to one group (OLD-AC) of male F-344 rats beginning at 16 months of age, while another group (OLD-CON) of rats was given water only during that period. The rats were maintained on this treatment throughout behavioral testing, which began at 22 months of age. Performance of the OLD-AC and OLD-CON rats was compared to that of young control (YG-CON) rats on the following set of tasks: spontaneous alternation in the arms of a T-maze, two-choice simultaneous discrimination in the stem of a T-maze, rewarded alternation in the arms of a T-maze, spatial discrimination and reversal on a circular platform, spatial working memory in the radial 8-arm maze, long-term memory in the 14-unit T-maze, and for preference of the light or dark chamber of a two-compartment box. AC improved the long-term memory performance in the split-stem T-maze and on the circular platform but had no discernable effects on performance of aged rats in the other tasks. Possible reasons for the selectivity of this agent's action on behavior are suggested.

Acetylcarnitine↗

PubMedDate not supplied

Acetyl-L-carnitine: behavioral, electrophysiological, and neurochemical effects.

Aged rats were chronically administered acetyl-L-carnitine (AC) for 10 months. During this period they were tested on learning and sensorimotor tasks and were then subsequently tested electrophysiologically to assess induction and decay rates of long-term synaptic enhancement (LTE) in the hippocampus. Four groups were tested: young controls (4 mo-con), middle-aged controls (16 mo-con), old controls (24 mo-con), and old AC-treated rats (24 mo-AC). After completion of electrophysiological testing, each rat was sacrificed and investigated for age- or drug-related changes in three neurotransmitter markers; including, NMDA-sensitive glutamate receptors, high affinity choline uptake, and adenosine receptor number in the neocortex, hippocampus or caudate nucleus. Aging impaired spatial learning and there was a robust positive correlation between NMDA receptors in the hippocampus and acquisition of the spatial learning task. Induction of hippocampal LTE was reduced in 24 mo-AC rats and NMDA receptor number and high-affinity choline uptake in the frontal cortex was increased. Several suggestions are offered to explain the action of AC on these neurobiological parameters in old rats.

Acetylcarnitine↗

PubMedDate not supplied

Age-related spatial reference and working memory deficits assessed in the water maze.

Aged rats have spatial memory deficits relative to young rats. The extent of these deficits in intermediate-aged rats is not well established. The present study examined the pattern of age-related changes in spatial reference and working memory in four ages of Fischer-344 rats. Place discrimination (PD) in the Morris water maze measured spatial reference memory. Repeated acquisition (RA), a discrimination in which the escape platform location varied from session to session, measured spatial working memory. Fischer-344 rats, 4 months, 11 months, 17 months, and 24 months of age, were tested. Compared to 4-month-olds, 24-month-olds were significantly impaired on all six PD measures of performance, 17 months were significantly impaired on five PD measures, and 11 months were significantly impaired on only one PD measure. Only 24-month-olds had a significant working memory impairment in RA relative to 4 months. Reference and working memory measures were distinct as assessed by a principal components analysis. The results indicate a nonlinear age-related spatial memory decline in Fischer-344 rats from 4 to 24 months of age.

Aging↗

PubMedDate not supplied

Within-subjects, parametric manipulations to investigate aging.

Parametric manipulation of experimental variables is important for both practical and theoretical reasons. Practically, age-related impairments in memory may be detected only at certain levels of difficulty. If the task is too simple, age-related cognitive impairments may not be sufficient to alter performance. If the task is too difficult, age-related cognitive impairments may not add significantly to the poor performance of younger controls. Thus, some intermediate level of difficulty is necessary to produce behavioral evidence on underlying age-related cognitive changes. Theoretically, parametric manipulations are important to identify the psychological processes responsible for the behavioral alterations. For example, consider the common finding of an age-related impairment in a delayed conditional discrimination task. If that impairment is produced by a primary deficit in recent memory, then the magnitude of the age-related impairment should increase with the length as the delay interval is increased, producing a statistical interaction between the age delay interval. Both the practical and theoretical considerations are illustrated with specific experiments, and have implications for the types of experimental design that can be most effective in demonstrating and explaining age-related changes in learning and memory.

Aging↗

PubMedDate not supplied

Individual differences in aging: behavioral and neurobiological correlates.

The goal of this experiment was to determine the correlations among different behavioral and neurobiological measures in aged rats. Aged Sprague-Dawley rats were given a battery of cognitive and sensorimotor tests, followed by electrophysiological assessment of sleep and biochemical measurements of various neurotransmitter systems. The behavioral tests included the following: Activity level in an open field; short-term and long-term memory of a spatial environment as assessed by habituation: spatial navigation, discrimination reversal, and cue learning in the Morris water pool; spatial memory in a T-maze motivated by escape from water; spatial memory and reversal on the Barnes circular platform task; passive avoidance; motor skills. Sleep was assessed by electrographic cortical records. The following neurotransmitter markers were examined: Choline acetyltransferase; the density of nicotinic, benzodiazepine and glutamine receptors in the cortex and caudate nucleus; endogenous levels of norepinephrine, dopamine, and serotonin in the cortex and hippocampus. The duration of bouts of paradoxical sleep was strongly correlated with several cognitive measures and selected serotonergic markers. This finding suggests that changes in sleep patterns and brain biochemistry contribute directly to deficits in learning and memory, or that the same neurobiological defect contributes to age-related impairments in sleep and in learning and memory.

Age Factors↗

PubMedDate not supplied

Life-long diet restriction failed to retard cognitive aging in Fischer-344 rats.

Although the beneficial effects of diet restriction on longevity and the retardation of many somatic age-related processes are well established, the answer to the question of whether anti-aging effects of diet restriction extend to the brain and cognitive function remains unclear. In the present study, the effects of long-term dietary restriction (60% of ad-libitum calories) on an age-related alteration of memory and sensorimotor function have been investigated in Fischer 344 male rats at four different ages: 6 months, 12 months, 18 months, and 24 months. A major drop in reference memory of DR and AL rats occurred at the age of 18 months. The performance deficits in working memory tasks were observed in both diet groups at the age of 24 months. These results indicate that diet restriction failed to provide protection against age-related deficits in memory. Although DR rats outperformed AL rats in sensorimotor tasks throughout the life-span, the slope of the declining function in DR rats paralleled those of AL rats, suggesting that diet restriction failed to alter the rate of aging in sensorimotor performance, as well.

Aging↗