Working memory test in the genetically hypertensive rats of Koletsky type and in the normotensive rats of Wistar strain.

The experiments were carried out in the adult normotensive rats of Wistar strain and in the genetically hypertensive rats which were developed by Koletsky; the experiments were performed in both sexes. For a testing of the working memory we have used the new session unique test elaborated by Ennaceur and Delacour. This test is based on the differential exploration of familiar and new objects. In the first trial rats are exposed to two identical objects (samples) and in the second trial, to two dissimilar objects, a familiar (the sample) and a new one. Between the trials one minute intertrial interval was used. The working memory test was used in two experimental arrangements. In the first one the animals two days before testing were allowed to explore the testing box (without any objects) two minutes each day. In the second arrangement no adaptation to the testing box was used. The optimal conditions for memory processes in the genetically hypertensive rats are attained after previous adaptation to the testing box. The optimal conditions for memory processes in the normotensive rats of Wistar strain were obtained when no adaptation to the testing box was used. Moreover, it was also found that the more intensive explorations of samples is registered in the first trial, the more intensive novelty preference in the second trial was obtained. The possible role of the level of behavioral activation in the working memory processes is discussed.

Validation of aversion towards open space and height as a measure of anxiety in the genetically based animal model of depression.

Experiments were performed in the adult normotensive rats of Wistar strain and in the genetically hypertensive rats of Koletsky type; measurements were carried out in both sexes. The behaviour of control and drug treated rats were traced in the holeboard and in the elevated plus-maze. In the control animals when compared to the normotensive rats of both sexes, the genetically hypertensive rats of both sexes show increased aversion towards open space and high in the elevated plus-maze (when the number of visits of centre and open arms is considered in the first session); the latter type of rats also show elevated total time of locomotor-exploratory activity in both sessions, reduced rate of intra-session habituation of locomotor-exploratory activity in both sessions, and decreased percentage of time spent head dipping in both sessions. Tranylcypromine treatment at the dose 5 mg/kg b. w. increased number of visits in centre and in open arms only in the second session in the normotensive males, and this drug shows decrease in the latter parameter in the second session in the genetically hypertensive females. Tranylcypromine increased time spent in centre and in open arms in the first session only in the genetically hypertensive males, in the second session this drug shows increase in time spent in centre and in open arms in the normotensive females and decrease in the genetically hypertensive females. Caffeine treatment at the dose 10 mg/kg b. w. remained without effect in both strains of rats and in both sessions in the elevated plus-maze, except the decrease in the number of entries in centre and in open arms in the first session in the normotensive females. Diazepam treatment at the dose 1 mg/kg b. w. shows "anxiolytic" effect i.e., increase number of visits and time spent in centre and in open arms in both sessions and in both sexes of the genetically hypertensive rats. Thus diazepam shown its "anxiolytic" effect in very profound and stable manner only in the animals which show CNS neurotransmitter abnormalities reminding the CNS neurochemical abnormalities in human forms of depression and anxiety. It is worthwhile to note that diazepam only in the latter mentioned strain of rats very profoundly elevates the percentage of time spent head dipping. Thus this drug elevates the reactivity towards stimuli which show biological sense for the rats, i. e., to look up the small and dark space. This type of reaction is decreased in the genetically hypertensive rats of both sexes relative to the control normotensive rats of Wistar strain.

Animal model of anxiety: the effect of methyldopa in the genetically hypertensive non-obese rats of Koletsky type and in the rats of Wistar strain.

The experiments were carried out in the adult normotensive rats of Wistar strain and in the genetically hypertensive rats which were developed by Koletsky; the experiments were performed in the both sexes. The behavior of control and methyldopa treated rats were traced in the holeboard and in the elevated plus-maze. In the control animals when compared to the normotensive rats of both sexes, the genetically hypertensive rats of both sexes show elevated aversion towards open space and height (when the number of visits of centre and open arms is considered), elevated locomotor-exploratory activity and reduced rate of habituation of the latter activity; the genetically hypertensive males than show reduced percentage of time spent head dipping relative to the normotensive males. Methyldopa decreases locomotor-exploratory activity and increases intra-session rate of habituation of the latter activity in the both strains of rats. This drug shows in the first session decrease in the normotensive males and increase in the genetically hypertensive rats of both sexes the percentage of time spent head dipping. Methyldopa shows in the first session increase in the number of entries in centre and in open arms in elevated plus-maze solely in the genetically hypertensive rats of both sexes. When time spent in centre and in open arms of the elevated plus-maze is taken into consideration, methyldopa shows in the normotensive males decrease and in the genetically hypertensive males increase.

Animal model of anxiety: the effect of chronic bromocriptine treatment in the genetically hypertensive rats of Koletsky type and in the normotensive rats of Wistar strain.

Experiments were performed in the adult normotensive rats of Wistar strain and in the genetically hypertensive rats developed by Koletsky, i.e., in the strain where it is decreased turnover-rate of diencephalomesencephalic norepinephrine, increased CNS cholinergic activity, cholinergic supersensitivity and reduced stress resistance. The behavior in control and in drugged animals was traced in holeboard and in elevated plus-maze. In the control animals, when compared to the normotensive rats of Wistar strain, the genetically hypertensive rats of both sexes show in the first session elevated locomotor-exploratory activity, lower rate of intrassession habituation of the latter activity; in the genetically hypertensive males in the first session there is reduced percentage of time spent head dipping. The latter type of animals show lower number of entries into centre and in open arms by forepaws and by all four feet in the first session; in the first session time spent in centre and in open arms by forepaws and by all four feet is increased in normotensive males relative to hypertensive ones. Chronic Bromocriptine treatment shows in all traced parameters strain dependence. The drug only in the genetically hypertensive rats reduced total time of locomotor-exploratory activity in both sessions, elevated rate of intrasession habituation of locomotor-exploratory activity in both sessions, elevated directed exploration in hole-board in both sessions, alleviated aversion towards open space and height in the elevated plus-maze in both sessions.

Animal model of anxiety: effect of chronic diazepam treatment in the genetically hypertensive rats of Koletsky type and in the rats of Wistar strain.

Experiments were performed in the adult normotensive rats of Wistar strain in the genetically hypertensive rats of Koltsky type. Diazepam at the dose of 1 mg/kg was applied for five days. The last two days of diazepam treatment the behavior of the animals was traced in holeboard and in the elevated plus-maze. In the control animals the genetically hypertensive rats of both sexes show elevated locomotor-exploratory activity in holeboard in both sessions, genetically hypertensive females show highest degree of directed exploration in holeboard when compared with the other groups of rats; in the elevated plus-maze the normotensive rats of both sexes show lower aversion towards open space and height in elevated plus-maze relative to genetically hypertensive rats. Diazepam only in the genetically hypertensive females increases in the second session locomotor-exploratory activity and reduced the inter-session habituation of the mentioned activity. Directed exploratory activity in holeboard was by diazepam treatment elevated predominantly in the genetically hypertensive rats. In the genetically hypertensive females diazepam caused inter-session sensitization in directed exploration. Considering the number of entries in centre and in open arms of the elevated plus-maze, diazepam in both strains irrespective of sex and session caused increase. Taking into account time spent in centre and in open arms of the elevated plus-maze, the strain dependent effect of diazepam is apparent, i.e., statistical significance of its "anxiolytic" effect was attained only in the genetically hypertensive rats.

Animal model of anxiety: the effect of chronic dihydroergotoxine treatment in the genetically hypertensive rats of Koletsky type and in the rats of Wistar strain.

The observations were carried out in the adult normotensive rats of Wistar strain and in the genetically hypertensive rats developed by Koletsky, i.e., in the strain where is decreased turnover-rate of diencephalo-mesecephalic norepinephrine, increased CNS cholinergic activity accompanied by cholinergic supersensitivity and reduced stress-resistance. The effect of dihydroergotoxine was traced in holeboard and in the elevated plus-maze. Chronic dihydroergotoxine treatment shows "anxiolytic" effect in the elevated plus-maze (i.e., this drug alleviates aversion towards open space and height), increases directed exploration, elevates the rate of habituation of the locomotor-exploratory activity at all, and elevates the rate of habituation of directed exploration especially. The drug in the above mentioned parameters shows very expressive dependent effect, i.e., the effect being more or solely expressed in the genetically hypertensive rats of Koletsky type. The results of our recent series of experiments again suggest that is is well founded to use for the screening of the drugs with potential anxiolytic effect the genetically hypertensive rats of Koletsky type, i.e., the strain which by its CNS neurotransmitter abnormalities resembles deviations observed in the patients suffering from anxio-depressive disorders.

Animal model of anxiety: effect of acute diazepam treatment in the older adult genetically hypertensive rats of Koletsky type and in the older adult rats of Wistar strain.

The experiments were performed in the older adult (10-14 months of age) normotensive rats of Wistar strain and in the genetically hypertensive rats which developed Koletsky; the experiments were performed in both sexes. The behavior of control and diazepam treated rats were traced in the holeboard and in the elevated plus-maze. In the control animals when compared to the normotensive rats of both sexes show increase in total time of locomotor-exploratory activity in holeboard. In control animals the lowest level of directed exploration was found in the genetically hypertensive males. The control genetically hypertensive males show also the highest aversion towards open space and hight in the elevated plus-maze. Diazepam increases directed exploration in the genetically hypertensive rats of both sexes; directed exploration in the normotensive rats is not influenced by diazepam or this drug caused decrease. Diazepam shows no effect in between-session habituation of directed exploration in the normotensive rats of both sexes; in the genetically hypertensive rats under diazepam treatment instead of between-session habituation of directed exploration there appears in the second session elevation of directed exploration. Diazepam treatment alleviates in the first session aversion towards open space and hight in the elevated plus-maze only in the genetically hypertensive rats of both sexes and in the normotensive males. In the second session statistically significant alleviation of aversion towards open space and hight was attained in both strains of rats, in both sexes and under the both doses of diazepam. Considering the different markers of aging, stress plasma corticosterone and/or diazepam induced hypothermia show tighter age dependence in the genetically hypertensive rats than in the normotensive rats of Wistar strain. On the other hand, the effect of diazepam on aversion towards open space and hight show closer age dependence in the latter type of rats.

Animal model of anxiety: effect of nicergoline in the genetically hypertensive rats of Koletsky type and in the rats of Wistar strain.

The experiments were performed in the adult normotensive rats of Wistar strain and in the genetically hypertensive rats of Koletsky type; both sexes were used. The behavior in control and in Nicergoline treated rats was traced in holeboard and in the elevated plus-maze. In the control animals, when compared to the normotensive rats of Wistar strain, the genetically hypertensive rats of both sexes show elevated aversion towards open space and hight in the elevated plus-maze, reduced time spent head dipping in holeboard. The genetically hypertensive rats show maximal neophobia in the first minute of the first session in the holeboard. Nicergoline at the dose of 8 mg/kg b. w. reduced the aversion towards the open space and hight in elevated plus-maze only in the genetically hypertensive rats of both sexes. Moreover, Nicergoline in the genetically hypertensive males alleviates neophobic hypoactivity, increase head-dipping in the first session, increases head-dipping in the genetically hypertensive females in the second session. Nicergoline also decreases total time of locomotor-exploratory activity on holeboard in the males of both strains in the first session, in the second session the same effect of Nicergoline was found in all groups of rats except the genetically hypertensive females.

Behaviour of the genetically hypertensive rats of Koletsky type in holeboard and in elevated plus-maze: effect of scopolamine and nicergoline treatment.

The experiments were performed in the adult normotensive rats of Wistar strain and in the genetically hypertensive rats which were developed by Koletsky (12); both sexes were used. The behavior in control and in Scopolamine and Nicergoline treated rats was traced in the holeboard and in the elevated plus-maze. In the control animals, when compared to the normotensive rats of Wistar strain, the genetically hypertensive rats of both sexes show elevated aversion towards open space and hight in the elevated plus-maze, reduced time spent head dipping in holeboard, reduced rate of habituation of locomotor-exploratory activity, and the elevated total time of locomotor-exploratory activity in holeboard. Scopolamine at dose 0.25 mg/kg b. w. and Nicergoline at dose 4 mg/kg b. w. reduced the aversion towards the open space and hight in elevated plus-maze only in the genetically hypertensive rats of both sexes. Both drug when applied simultaneously show mutual potentiation in the genetically hypertensive rats. Both drugs when applied separately or simultaneously caused elevation of time spent head dipping, i. e., elevation of directed exploration. Nicergoline caused decrease and Scopolamine caused increase of total time of exploratory activity in holeboard. Nicergoline increases the rate of habituation of the locomotor-exploratory activity in the males of normotensive rats and in the genetically hypertensive rats of both sexes. Scopolamine remained without effect in the normotensive rats of both sexes, elevated the rate of habituation in the genetically hypertensive males.

Animal model of anxiety: effect of acute diazepam treatment in the genetically hypertensive rats of Koletsky type and in the rats of Wistar strain.

The experiments were carried out in the younger adult (3 to 5 months of age) normotensive rats of Wistar strain and in the genetically hypertensive rats which were developed by Koletsky; the experiments were performed in both sexes. The behaviour of control and diazepam treated rats were traced in the holeboard and in the elevated plus-maze. In the control animals when compared to the normotensive rats of both sexes, the genetically hypertensive rats of both sexes show elevated aversion towards open space and hight (when the number of visits of centre and open arms is considered), and elevated total time of locomotor-exploratory activity; the hypertensive males show decrease and female increase in time spent and in number of head-dipping. Diazepam at both doses (0.5-1.0 mg/kg b. w.) alleviates aversion towards open space and hight in the elevated plus-maze only in the genetically hypertensive rats. Directed exploration (head-dipping) was increased in the genetically hypertensive rats of both sexes at both doses of diazepam; at higher dose directed exploration was decreased in the normotensive males. Diazepam shows no effect in the between-session habituation of directed exploration in the normotensive rats of both sexes; in the genetically hypertensive rats instead of the between-session habituation of directed exploration, in the second session (relative to the first one) there appeared elevation of directed exploration.

Animal model of anxiety: effect of metergoline in the genetically hypertensive rats of Koletsky type and in the rats of Wistar strain.

The experiments were carried out in the adult normotensive rats of Wistar strain and in the genetically hypertensive rats of Koletsky type; both sexes were used. The behavior in control and in druged animals was traced in new environment, in holeboard and in elevated plus-maze. In the control animals, when compared to the normotensive rats of Wistar strain, the genetically hypertensive rats of both sexes show elevated neophobia, reduced rate habituation of exploratory activity; the males of the latter strain then show reduced rate of rearing in holeboard and elevated aversion towards open space and hight in the elevated plus-maze. Metergoline at the dose 8 mg/kg b.w. normalized the rate of habituation of exploratory activity, reduced the aversion towards the open space and hight in elevated plus-maze in the genetically hypertensive rats of both sexes in the first session, in the males of normotensive rats in the second session. Moreover, Metergoline elevated directed exploration in the normotensive males and in both sexes of the genetically hypertensive rats and elevated rearing in the males of the genetically hypertensive rats. It can be concluded that Metergoline represents a potential anxiolytic drug.