CC BY
37STH MULTIDISCIPLINARY INTERNATIONAL
Conference of Biological Psychiatry
«Stress and Behavior»
Proceedings of the 9th International Multidisciplinary Conference «Stress and behavior» Saint-Petersburg, Russia, 16-19 May 2005 Editor: Allan V. Kalueff, PhD
CONFERENCE ABSTRACTS
4. EXPERIMENTAL MODELS:
M.A. DERYAGINA MEMORIAL SYMPOSIUM
MORPHOCHEMICAL PECULIARITIES OF AUGUST RATS’ HIPPOCAMPUS UNDER DOPAMINERGIC SYSTEM HYPER FUNCTION
A.V. Sergutina, L.M. Gershtein Brain Research Institute RAMS, Moscow, Russia Relationships between the behavior and morphochemical peculiarities of human and mammalian brain are presently studied on rat and mouse genetic models. August rats are regarded as a genetic model of increased anxiety with frequent neuroses and psychosis. Neurochemical reaction on stress is realized in the expression of early response genes and the changes of neurotransmitter and protein metabolism. Marked activation of early genes in response to chronic stress was demonstrated in the limbic structures (Sudakov, 1998; Umryukhin, 2000) playing the leading role in the emotional reactions. To further study this problem, dopaminergic system hyperactivity was experimentally induced in August rats by chronic L-DOPA or amphetamine administration. Some protein and neurotransmitter metabolism indices were determined in the hippocampus (CA1 and CA3 fields) during L-DOPA treatment. Protein content and the area of field CA 3 neurons were measured interferometrically during amphetamine treatment. Quantitative cytochemical investigation of protein (aminopeptidase — AMP, glutamate dehydrogenase — GDH) and neurotransmitter (monoamine oxidase: substrates — tryptamine and
5-hydroxytryptamine — MAO T and MAO 5-HT; acetylcholinesterase —AChE) metabolizing enzymes’ activities was performed. August rats were decapitated under ether anesthesia. The control animals were injected with saline. Experimental animals received L-DOPA (Madopar-125 25.5 mg/kg daily for 2 weeks). Enzymes’ activity was measured in cryostat sections of the brain with further quantitative evaluation in relative optical units using LUMAM-I 3 microscope (Russia). For cytophotometric studies the rats were treated with 2.5 mg/kg amphetamine for 3 weeks. After decapitation the brain was fixed in Carnoi fluid and 7 mm- slices were prepared from paraffin-embedded tissues. The dry mass of the dense substances that in fixed material reflects the protein content in brain structures (Brodsky, 1966) was measured with Interfaco interferometer (Gershtein, 1979). Ocular micrometer was used to measure the area of the profile fields of the cytoplasm and nucleus of the neural cell. L-DOPA did not affect AMP, GDH, MAO 5-HT and AChE activities either in CA3 or CA11 fields in August rats. MAO T activity increased under L-DOPA both in CA3 and CA1 fields. Amphetamine administration increased cytoplasmic and nuclear areas in CA 3 neurons of the hippocampus. Under the experimental conditions protein content as well as its concentration in the cytoplasm and nuclei were increased. The distribution profiles of the parameters studied revealed a similar response to amphetamine of all the field CA 3 neurons in August rats’ hippocampus. Hippocampal CA1 field is regarded in the literature as an «informatic», and CA3 — as «regulatory». Thus, metabolic changes in CA3 field may reflect the changes in the limbic system in general. MAO substrate tryptamine recently drew attention because of its possible modulatory role in the function of serotonergic receptors. It might be supposed that under the conditions of L-DOPA induced dopaminergic system activation August rats should experience rearrangement of serotonergic neurotransmission that participates in the processes of leaning, memory and emotional activity of the animals in both hippocampal fields. The increase of protein indices and the sizes of the CA3 neurons under amphetamine
ISSN 1606-8181
indicates augmentation of their functional activity. In the open field tests, after L-DOPA, August rats demonstrated a decrease of the horizontal activity and behavioral manifestations of fear. Altered behavior of these animals under dopaminergic hyperfunction may be explained by the activation of serotonergic system in their brain — the finding that was confirmed on subcellular level for chronic amphetamine administration (Dovedova, Khrustalev, 2004). We suggest that in stressful situations, the systemic reactions in animals with increased anxiety may originate from the depressive action of serotonergic system on brain structures responsible for the emotional and information-processing domains of their behavior. Functional activity of these structures apparently correlates with the accumulation of proteins in their neurons. The study was supported by the RFBR grant 03-04-4835.
ISSN 1606-8181
