Role of the mesotelencephalic dopamine system in learning and memory processes in the rat

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Abstract

The effects of lesioning the ventral tegmental area or substantia nigra pars reticulata by means of bilateral microinjections of two doses of kainic acid (50 ng/250 nl and 100 ng/500 nl) or 6-hydroxydopamine (8 μg/4 μl) were investigated to clarify the role of the mesotelencephalic dopamine system in learning and memory processes. Our findings suggest that ventral tegmental area and substantia nigra dopaminergic neurons play an important role in retention of both short-term memory, tested in the Y-maze task and long-term memory evaluated with the multi-trial passive avoidance test, without affecting memory acquisition. As compared to short-term memory, long-term memory is more susceptible to the decreased dopamine level in nervous structures involved in processing and storage of information.

Introduction

The mesotelencephalic dopamine system is generally divided into three components: mesostriatal (also commonly called nigrostriatal), mesolimbic and mesocortical (White, 1996). The mesostriatal dopamine fibres arise mostly from the substantia nigra pars compacta projecting predominantly to the caudate–putamen (Fallon, 1988). The mesolimbic dopamine fibres arise predominantly from the ventral tegmental area with a minor component originating in various parts of the substantia nigra. These mesolimbic dopamine fibres project mostly to the nucleus accumbens, amygdala, nucleus of stria terminalis, lateral septal area, etc. The mesocortical dopamine fibres predominantly arise from the ventral tegmental area, although some originate from different parts of the substantia nigra. These fibres primarily innervate the medial prefrontal cortex, the anterior cingulate cortex and the suprarhinal cortex (Gardner and Ashby, 2000).

In the present study, we investigated the role of the dopaminergic neuronal system and other neurons from the substantia nigra pars reticulata and ventral tegmental area in short- and long-term memory by injecting 6-hydroxydopamine, a specific neurotoxin for dopamine neurons, or kainic acid (which destroys only the soma of different type of neurons without affecting the passing fibres). Our data suggest that mainly dopaminergic neurons in both substantia nigra and ventral tegmental area have a role in short- and long-term memory retention, the role of ventral tegmental area being more prominent than that of substantia nigra. In contrast, the acquisition of memory was not impaired by lesions of ventral tegmental area and substantia nigra.

Section snippets

Materials and methods

Male Wistar rats weighing 250–300 g at the start of the experiment were used. The rats were treated in accordance with the Guidelines for Animal Experiments of the “Al.I.Cuza” University and of the U.S. National Institute of the Health Guide for the Care and Use of Laboratory Animals. The rats were housed three per cage with free access to food and water under controlled laboratory conditions (a 12-h light/dark cycle with lights on at 8:00 a.m., 22±0.5 °C)

Histological verifications

After chemical lesions the rats recovered quickly and gained weight by 1 week. Fig. 1 illustrates the rostrocaudal extension of the mean lesion sites of the substantia nigra and ventral tegmental area.

In the majority of substantia nigra-lesioned rats (9/12), the point of the syringe needle was positioned symmetrically in the central part of the substantia nigra pars reticulata and the lesions extended from −5.3 to −5.8 mm posterior to bregma, without any significant damage to adjacent

Discussion

Our experimental data suggest that ventral tegmental area dopaminergic neurons have a crucial role in short- and long-term memory retention without affecting memory acquisition. Substantia nigra dopaminergic neurons have a similar role, the effect of ventral tegmental area being more prominent. Because testing of long-term memory supposes avoidance of a pain stimulus delivered in the acquisition period in the dark compartment of the passive avoidance apparatus, the retaining of information

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