Biomedical subjects

B A Wirsching

Publications and source records attributed to B A Wirsching.

6 recordsLinked to original sources

PubMed1995

Physostigmine, but not 3,4-diaminopyridine, improves radial maze performance in memory-impaired rats.

The results of some studies suggest that 3,4-diaminopyridine (3,4-DAP), a drug that enhances the release of acetylcholine, may improve memory. The present study examined the ability of 3,4-DAP to reverse the memory impairment produced by scopolamine and the ability of 3,4-DAP and physostigmine to reverse the memory impairment produced by quinolinic acid lesions of the nucleus basalis magnocellularis (nbm) in rats. Mnemonic functioning was assessed with the use of a partially baited eight-arm radial maze. Entries into arms that were never baited were defined as reference memory errors; entries into baited arms from which the food already had been eaten were defined as working memory errors. In Experiment 1, 0.1 mg/kg scopolamine produced a significant increase in working and reference memory errors. Various doses of 3,4-DAP had no significant ameliorative effect on the mnemonic deficit. In Experiment 2, cholinergic function was impaired using a unilateral intra-nbm injection of quinolinic acid (120 nmol in 1.0 microliter). These lesions reduced the levels of the cholinergic marker, choline acetyltransferase, in the cortex by more than 40%. Results showed that the nbm lesion animals were significantly more impaired on the working than reference memory component of the task. Physostigmine (0.01, 0.05, 0.10, 0.20, 0.50 mg/kg) dose-dependently decreased the number of working but not reference memory errors. 3,4-DAP (10(-8), 10(-6), 10(-4), 10(-2), 10(0) mg/kg) had no reliable effect. It was concluded that physostigmine, but not 3,4-DAP, ameliorates memory impairments following decreases in cholinergic function.

4-Aminopyridine↗

PubMed1989

Kynurenic acid protects against the neurochemical and behavioral effects of unilateral quinolinic acid injections into the nucleus basalis of rats.

It has recently been demonstrated that kynurenic acid (KYN), an endogenous tryptophan metabolite, provides almost complete protection against the neurotoxic and mnemonic effects of another tryptophan metabolite quinolinic acid (QUIN) on the cell bodies of the nucleus basalis magnocellularis (nbm). The present study further investigated whether unilateral coinjections of KYN and QUIN into the rat nbm antagonized the effects of QUIN alone. Food-deprived rats were pretrained on an eight-arm radial maze, with four arms baited, until choice accuracy stabilized to greater than or equal to 87% correct. Postoperatively, rats were tested on the radial maze for 32 consecutive days. Feeding behavior and locomotor activity were also measured to determine if nonassociative factors accounted for any observed behavioral deficits. QUIN lesions resulted in significantly more working and reference memory errors compared with sham-operated and coinjected animals, which did not differ significantly from each other. There were no reliable group differences in amount of food eaten or locomotor activity. The QUIN group had a reliable decrease in cortical choline acetyltransferase, with no significant changes for the sham and coinjected groups. Results confirm that KYN antagonizes the neurotoxic and mnemonic effects of QUIN alone and suggest that the memory deficits induced by nbm lesions cannot be solely attributed to changes in feeding or locomotor activity.

Animals↗

PubMed1989

Animal studies of brain acetylcholine and memory.

Memory loss is a common feature of aging in the human but not all memories are equally lost. Usually the loss is more severe for the memory of recent events and information rather than the memory of remote events and information. Associated with memory losses of this type is a reduction in levels of cortical acetylcholine and a loss of cholinergic cells of the nucleus basalis magnocellularis. In the rat it is possible to assess two types of memory analogous to recent and remote memories in humans. Reference memory would refer to information concerning the task that is invariant from trial to trial. Working memory would refer to information that changes from trial to trial. In support of the hypothesis that decreases in cholinergic function lead to a differential impairment of working memory, rats trained in this task and given scopolamine showed a specific increase in working memory errors. In more recent studies rats have been trained in a task and then given unilateral neurotoxic lesions of the NBM. These results raise the intriguing possibility that degeneration of the NBM and associated memory impairment seen in aging and in Alzheimer's disease may be related to a change in the ratio of these or related endogenous tryptophan metabolites.

Acetylcholine↗

PubMed1986

Effects of altered cholinergic function on working and reference memory in the rat.

Many data suggest that the brain's cholinergic neurons participate in the control of memory and it has been suggested that cholinergic systems are involved differentially in working and reference memory. To test this hypothesis the effects on memory of unilateral injections of the neurotoxins, quinolinic acid or kainic acid into the cortically projecting cholinergic cells of the nucleus basalis magnocellularis (nbm) were evaluated. In experiment 1, quinolinate-injected (n = 7) and sham-operated (n = 7) rats were tested in a T-maze alternation task that requires working memory. Lesion rats performed significantly more poorly than shams and subsequent biochemical assays of cortical choline acetyltransferase (CAT) activity revealed significant reductions in the lesion rats. In experiment 2, kainate-injected (n = 9) and sham-operated (n = 8) rats were trained in an eight-arm radial maze with only four arms baited. Lesion rats made significantly more working memory errors (entries into baited arms from which the food had already been collected) than reference memory errors (entries into never baited arms). CAT assays showed that the lesion led to a decrease in cortical CAT with no significant change in hippocampal CAT. The results of these studies support the hypothesis that cholinergic neurons of the basocortical system may be differentially involved in working and reference memory.

Animals↗

PubMed1985

Functional and neurochemical cortical cholinergic impairment following neurotoxic lesions of the nucleus basalis magnocellularis in the rat.

The effect of kainic and quinolinic acid on cortical cholinergic function was examined following injections of these agents into the nucleus basalis magnocellularis (nbm) or into the frontoparietal cortex. The release of cortical 3H-acetylcholine (3H-ACh), high affinity choline uptake (HACU) and acetylcholinesterase was measured 7 days following injections of saline (control), kainic acid (4.7 nmoles) and quinolinic acid (60, 150 and 300 nmoles) into the nbm. These cortical cholinergic parameters were also examined after injections of saline (control), kainic acid (9.4 nmoles) and quinolinic acid (300 nmoles) into the fronto-parietal cortex. The release of 3H-ACh, HACU and AChE was significantly reduced in animals injected with kainic or quinolinic acid into the nbm. Histological examination of stained sections showed a loss of cell bodies in the region of the nbm and the globus pallidus. The size of the lesion produced by quinolinic acid was proportional to the dose injected into the nbm. In animals injected with kainic acid or quinolinic acid into the cerebral cortex, the release of 3H-ACh, HACU and AChE was not significantly reduced when compared with control animals, although histological examination of stained cortical sections showed a marked loss of cortical neurons. The results show that quinolinic acid, an endogenous neuroexcitant, produces a deficit of cholinergic function similar to that described in the cortical tissue of patients with senile dementia of Alzheimer's type. The toxic effects of quinolinic acid on cortical cholinergic function are due to its action on cholinergic cell bodies in the nbm.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1984

Differential effects of scopolamine on working and reference memory of rats in the radial maze.

Anticholinergics have often been found to impair choice accuracy in the radial maze. Some researchers have suggested that this indicates involvement of cholinergically innervated structures in cognitive mapping while others argue that these structures mediate working memory. However, most results are open to either interpretation since the baiting method did not allow a distinction between reference and working memory errors. To further test these hypotheses this study examined the effects of systemic scopolamine on radial maze performance, using a 4-out-of-8 baiting procedure. Food-deprived Wistar rats were pretrained until working memory choice accuracy stabilized to a criterion of 87% or better. Scopolamine (0.1, 0.4 and 0.8 mg/kg, IP, 30 min before a session) significantly increased the number of working memory errors (re-entries into baited arms) whereas reference memory errors (entries into never baited arms) did not change significantly. Observed deficits appeared not to be attributable to a drug-induced disruption of motivational systems. Results confirm the behavioural similarities between the memorial effects of hippocampectomy and anticholinergics, and implicate cholinergically innervated structures in working memory.

Animals↗