9th 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 1. PSYCHOPHARMACOLOGY

COMPARISON OF DIFFERENT AMPHETAMINE DOSES ACTION ON THE BRAIN METABOLISM OF RATS WITH DIFFERENT

BEHAVIORAL PATTERNS

D.A. Khrustalyov, E.L. Dovedova Brain Research Institute, Moscow, Russia Peculiarities of animal behavior are known to be related with both genetic predisposition and different influences that in great extent depend on CNS state. Rats of various strains are known to differ in reflection activity, sensitivity to external influences and stress, which are predisposed by structural-functional and metabolic features of the brain. Experimental influences selectively influencing upon neurotransmitters' metabolism help to create the models of some pathological conditions. Thus amphetamine administration alters neurotransmitter activity and affects mobility and behavior. Literature data confirm that long-term usage or high doses of amphetamine administration induce schizophrenia-like states. However, there are few data concerning the action of different amphetamine doses on the brain metabolism of rats with different behavioral patterns. Comparative investigation of the brain of two rats strains: Wistar (resistant) and August (susceptible to stress) was performed. The activities of the enzymes of neurotransmitter catabolism — MAO A and B — were studied in subfractions of the cortex and caudate nucleus.

Methods: Mature male Wistar and August rats were used in the experiments. Rats received a single I.p. amphetamine injection (1—2.5 mg/kg) and 60 min later were decapitated under ether anesthesia. Mitochondrial fractions were isolated by differential centrifugation. MAO A activity was determined according to Popov (1971) at 250 nm (substrate — serotonin). MAO B activity was determined according to Gorkin (1981) at 450 nm (substrate — para-nitrophenilethylamine). The total protein in content in mitochondrial fractions was determined by Lowry's method at 750 nm. Results were calculated in appropriate activity units per 1 mg of protein and represented as percentiles of control level (100%).

Results and discussion: A single amphetamine injection resulted in behavioral alterations of both strain rats such as a loosing of the sense of fear (entrance to field center), mobility activation, although the degree of these changes was different (Wistar rats were thrice as active as August rats). Wistar rats showed more reduction of exploration than did August rats. Orientation reaction of Wistar rats increased by 12% (vs. only 5% in August rats). August rats had pendulum-like movements of head, turning around, and tendency to catalepsy. Such behavioral alterations after a short-term amphetamine administration were seen for all doses of the drug, but were more pronounced at 2.5 mg. Biochemical study has also revealed differences between the rat strains. MAO B activity in the cortex of Wistar rats brain increased up to 115%, in the caudate nucleus up to 130% (vs. controls after amphetamine at 2.5 mg), whereas it did not change in brain structures of August rats: 107 and 98%, respectively. Study of serotoninergic system by MAO A activities under amphetamine at 2.5 mg showed that MAO A activity decreased up to 80% in the cortex and up to 90.1% in the caudate nucleus of Wistar rats vs. controls, whereas it increased in the August rats brain: 125 and 136.4% respectively. Amphetamine at 1 mg leads to MAO B activation in the Wistar rats brain: 127.1% cortex, 112% caudate nucleus (vs. controls). However, MAO B increased up to 107.9% and 151.9% respectably under similar conditions (1.0 mg) in the August rats. MAO A activity reduced up to 64% in the cortex and up to 80% in the caudate nucleus of Wistar rats brain after single amphetamine injection at 1 mg/kg. MAO A activity strongly decreased in August rats brain: 63.2% and 65.4% respectably, vs. control. Thus, small dose of amphetamine leads to similar changes in enzymes activity of both strain rats manifest in MAO A activity reduction and MAO B activation. Using higher dose of amphetamine (2.5 mg/kg) showed anomaly, reverse changes in

Psychopharmacol. Biol. Narcol. 2005. Vol. 5, N 2. P. 887

Psyhopharmacology & biological narcology

ISSN 1606-8181

enzymes activity in the brain structures of August strain rats. This particularly concerns MAO A activity, possibly indicating intensification of serotoninergic system and inhibitory mechanism in general. Activation of dopaminergic system was demonstrated in Wistar rats' brain, whereas August rats showed activated serotoninergic system. High sensitivity of August rats might be associated with lower activity of serotoninergic system enzymes under normal conditions. Apparently, dose 2.5 mg/kg is optimal for Wistar rats, but it is toxic for stress-predisposed August rats. Thus, it may be suggested that predisposed to stress and emotional reactivity August rats also display anomalies in functioning of neurotransmitters systems of the brain not only under normal conditions, but under influences of unfavourable factors especially, in particular amphetamine action. This study was supported by grant 03-04-48350 from the Russian Foundation for Basic Research.

Psychopharmacol. Biol. Narcol. 2005. Vol. 5, N 2. P. 887

Psyhopharmacology & biological narcology

ISSN 1606-8181