Vesselin D. Petkov

Asymmetry in behavioral responses to cholecystokinin microinjected into rat nucleus accumbens and amygdala

The behavioral responses of rats to uni- or bilateral microinjections of the octapeptide cholecystokinin (CCK-8) into the left and/or right or both nucleus accumbens (NA) or amygdalae were studied. There were two main findings of effects of microinjections of CCK-8 into NA. First, bilateral injections of CCK-8 into NA dose-dependently decreased the horizontal activity. The second more important finding was that CCK-8 at a specific dose (0.01 micrograms) injected into the right NA increased the number of horizontal movements 6-fold as compared to the injection into the left NA. Neither uni- nor bilateral injections of CCK-8 into NA at all doses used induced changes in the vertical movements. CCK-8 injected into left, right or both amigdalae increased locomotion at the lowest dose (0.01 microgram), while at the high doses (0.5 and 1.0 microgram) it significantly decreased it. The plus-maze test confirmed the anxiogenic effect of CCK-8 (0.01 microgram) injected into amigdalae. CCK-8 exerted a favorable effect on learning and memory (shuttle-box) when injected into the left but not into the right amygdala. Injection of CCK-8 (0.01 micrograms) into left amygdala provoked a 4-fold increase of the number of avoidances as compared to the microinjection into the right amygdala.

Age-related changes in brain neurotransmission.

In experiments on 2-, 10- and 22-month-old rats it was found that the Bmax values of dopamine (DA2), serotonin (5-HT1) and enkephalin (Enk) receptors as well as the 5-HT level in the three brain regions (cortex, striatum and hypothalamus) decreased with age; the DA level in the brain cortex and striatum and the noradrenaline (NA) content in the brain cortex decreased, while the NA level in the striatum and the 5-hydroxyindolacetic acid (5-HIAA) level in the brain cortex and the striatum as well as the MAO-T and MAO-A activities in the three brain structures increased. It is suggested that these and other changes observed in brain neurotransmission are an important element in the neurochemical bases of the age-related changes in behavior.

Changes in brain biogenic monoamines induced by the nootropic drugs adafenoxate and meclofenoxate and by citicholine (experiments on rats)

1. The effects of Adafenoxate (Adf), meclofenoxate (Mf) and citicholine (CCh) administered at a daily dose of 100 mg/kg for 7 days on the levels of noradrenaline (NA), dopamine (DA) and serotonin (5-HT) in the frontal cerebral cortex, striatum, hippocampus and hypothalamus of rats were studied. 2. Adafenoxate increased the NA level in the striatum and decreased it in the hypothalamus; it increased the DA level in the cerebral cortex and hypothalamus and decreased it in the striatum; it increased the 5-HT level in the cerebral cortex and decreased it in the hippocampus. 3. Meclofenoxate decreased the NA level in the cerebral cortex and hypothalamus; it increased the DA level in the hippocampus and hypothalamus and the 5-HT level in the cerebral cortex, striatum, hippocampus and hypothalamus. 4. Citicholine increased the NA level in the cerebral cortex and hypothalamus; it increased the DA level in the striatum and the 5-HT level in the cerebral cortex, striatum and hippocampus. 5. An attempt is made to explain some similarities and differences in the behavioral effects of the drugs tested (and those observed in other studies) by the changes they induce in brain biogenic monoamines.

Hippocampal asymmetry in the behavioral responses to the 5-HT1A receptor agonist 8-OH-DPAT

The present study examined the behavioral responses of rats to unilateral and bilateral injections of the selective serotonin 1A (5-HT1A)-receptor agonist 8-hydroxydipropylaminotetralin hydrobromide (8-OH-DPAT) 1 microgram into the hippocampal CA1 area of male Wistar rats. 8-OH-DPAT increased locomotor activity, which was most pronounced with injections into the left hippocampus. The agonist impaired learning and memory (shuttle-box), especially when injected into the right hippocampus. The elevated plus-maze experiments showed that neither left nor right nor bilateral hippocampal injections of 8-OH-DPAT produced any anxiogenic effect. However, with Vogels conflict test, right injections of 8-OH-DPAT produced anxiety. The present study has revealed hippocampal asymmetry in the behavioral responses to the 5-HT1A-receptor agonist 8-OH-DPAT.

Behavorial responses to the 5-HT1A receptor antagonist NAN190 injected into rat CA1 hippocampal area

1. Behavioral responses to unilateral and bilateral microinjections of the 5-HT1A receptor antagonist, NAN190 [1-(2-methoxyphenyl)-4-[4-(2-phthalimido) butyl]piperazine hydrobromide] (1 microgram), into the hippocampal CA1 area of male Wistar rats were studied. 2. NAN190 decreased locomotor activity (the number of horizontal and vertical movements). The effect was most pronounced with microinjections of NAN190 into the right hippocampus. 3. Microinjections of NAN190 facilitated learning and memory in shuttle-box testing. 4. Microinjections of NAN190 had an anxiogenic effect in elevated plus-maze experiments and Vogels conflict test. 5. The different behavioral responses to left and right microinjections of NAN190 in some of the behavioral tests suggest functional asymmetry of 5-HT1A receptors in the CA1 hippocampal area.

Enkephalin receptor changes in rat brain during aging

In experiments on 2-, 10- and 22-month-old rats, it was found that the number (Bmax) of brain enkephalin (Enk) receptors decreased with aging. The Bmax values in the cortex of 22-month-old rats decreased by 57%, in the striatum by 33% and in the hypothalamus by 84% as compared to those in 2-month-old rats. The Enk receptor sensitivity in the brain of aged rats also decreased (increased Kd). It is suggested that the changes in opiate receptors play a role in the age-related reduction of the adaptive capacity of the organism. The studies with repeated administration of L-dopa or haloperidol provided further evidence for interactions between opiate and dopaminergic systems.

Age-related changes in brain biogenic monoamines and monoamine oxidase

In experiments on 2-, 10- and 22-month old rats, it was found that essential age-related changes occurred in the brain level of biogenic monoamines (BMA) and in the monoamine oxidase (MAO) activity. In 22-month old rats the levels of dopamine (DA), noradrenaline (NA) and serotonin (5-HT) markedly declined in most of the brain structures studied. 5-HT significantly decreased in the frontal cortex, striatum and hypothalamus. DA decreased in the cerebral cortex and striatum and NA in the cerebral cortex. However, the NA level in the striatum of 22-month old rats was increased as compared to that in 2-month old rats. In most cases we observed significant differences (a decrease mainly) also in the level of BMA in 22-month old rats as compared to 10-month old rats. The differences, if any, in the BMA levels between 10- and 2-month old rats were less pronounced. The level of 5-hydroxyindole acetic acid (5-HIAA) in the cerebral cortex and striatum of 22-month old rats was significantly higher as compared to that in 2-month old rats. The MAO-T and MAO-A activities in the brain structures studied were significantly higher in 22-month old rats as compared to those in 2-month old rats. The possibility that the age-related changes in brain neurotransmission might be an important element in the neurochemical basis of some behavioral changes in advanced age is considered.

Age-related changes in rat brain muscarinic receptors and β-adrenoreceptors

Abstract 1. 1. In experiments on 2-, 10- and 22-month old rats, it was found that the Bmax values for muscarinic receptors and β-adrenoreceptors increased in the cerebral cortex, striatum and hippocampus of 10-month old rats as compared to those in 2-month old rats. 2. 2. The Bmax values for both receptor types significantly decreased in the same brain structures of 22-month old rats as compared to those in 10-month old rats. In the striatum and hippocampus of 22-month old rats the binding capacity decreased as compared also to those in 2-month old rats. 3. 3. In the hypothalamus there was also a tendency towards increasing the binding capacity of 10-month old rats and towards decreasing the binding capacity of 22-month old animals only for muscarinic receptors. The βmax of beta-adrenoreceptors remained unchanged in all age groups studied. 4. 4. The receptor affinity of both receptor types was in most cases unaltered with advancing age. The Kd values were slightly increased only in the striatum and hippocampus of 22-month old rats as compared to 10-month old rats. 5. 5. The role of age for the changes in the activity of brain muscarinic and β-adrenoreceptor systems is discussed.

The 5-HT2 receptor antagonist ketanserine prevents electroconvulsive shock- and clonidine-induced amnesia

The 5-HT2-selective antagonist ketanserine was examined for its ability to prevent electroconvulsive shock (ECS)- or clonidine-induced performance deficit in the passive avoidance situation (step-down) in rats. The posttrain intraperitoneal injection of ketanserine at doses of 3 and 10 mg/kg prevented the ECS- or clonidine-provoked amnesia upon retention tests given 3 h, 24 h, and 7 days after training. The present data favor the view that the selective modification of 5-HT2 receptors after training can prevent the performance deficit in step-down-trained rats and suggest a role of the 5-HTergic neurotransmitter system in memory. The results of this study further suggest that 5-HTergic receptor antagonists might be useful in treatment of cognitive disorders.

Age-related changes of the effects of a group of nootropic drugs on the content of rat brain biogenic monoamines

1. The changes in the levels of brain biogenic monoamines (BMAs) after chronic (7 days) treatment with piracetam, aniracetam and structural analogues of aniracetam (p-H, p-F, p-Cl, p-P and m-D) were studied in young and old rats. 2. An age-related significant decrease in the BMA content was established in old rats. 3. Most of the investigated compounds increased the level of one or other BMA in one or other of the brain structures studied. This elevation was predominantly established in old rats. 4. The present results and those from previous behaviour studies show that elevation of one or more of the BMA levels in one or more brain regions plays a beneficial role in the realization of their effects on the processes of learning and memory.