Stiliana Belcheva

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.

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.

Antinociceptive effect of somatostatin microinjected into caudate putamen.

The effects of somatostatin microinjected bilaterally and unilaterally (left or right) at a dose of 10, 50 and 100 ng into the caudate putamen of male Wistar rats on nociception (analgesy-meter test) were studied. Somatostatin injected into caudate putamen resulted in analgesia. Bilateral microinjections of somatostatin significantly increased the pain threshold in a dose-dependent manner, i.e. somatostatin exerted antinociceptive effect. The pain threshold after left-side microinjections was significantly higher than that after injections into right-side. These findings suggest antinociceptive and asymmetric effects of somatostatin on pain in the caudate putamen.

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.

Hippocampal asymmetry in serotonergic modulation of learning and memory in rats.

The modulation of learning and memory after left or right microinjections of the selective 5-HT1A receptor agonist 8-OH-DPAT and of the 5-HT1A receptor antagonist NAN190 into the hippocampal CA1 area of male Wistar rats was studied. Microinjections of 8-OH-DPAT (1 µg) into the right or left CA1 hippocampal area produced a significant decrease in the number of avoidances in a shuttle box. The impairing effect of 8-OH-DPAT was more pronounced when injected into the right hippocampus compared to the left one. Microinjections of NAN190 (1 µg) into the right or left CA1 hippocampal area produced a significant increase in the number of avoidances in a shuttle box. Right microinjections of NAN190 increased the number of avoidances more strongly than compared to left injections. These effects on learning and memory were more pronounced after injection of either of the serotonergic agents into the right CA1 hippocampal area compared to the left. The stronger memory-modulating effect after injection of 8-OH-DPAT or NAN190 into the right CA1 hippocampal area suggests a rightward bias in the rat.

Differential involvement of hippocampal vasoactive intestinal peptide in nociception of rats with a model of depression

The effects of VIP microinjected unilaterally (left or right) into the hippocampal CA1 area at a dose of 10 and 100 ng or bilaterally (10 ng), on nociception of male Wistar rats with a model of depression (bilateral olfactory bulbectomy-OBX) were studied. Nociception was examined applying mechanical pressure on the left hind paw of the rat (analgesy-meter test). It was found that in OBX rats the pain threshold is increased. VIP showed differential effects depending on the side and dose of administration. The pain threshold after left-side microinjections of VIP into the hippocampal CA1 area of OBX rats was significantly higher than that after injections into right-side. There are no significant differences between right-side VIP-treated and OBX rats. Bilateral microinjections of VIP also exerted antinociceptive effect. These findings suggest that the hippocampal lateralized antinociceptive effect of VIP in OBX rats depends on the hemisphere of injection and suggest that VIP-ergic neurons in the hippocampal CA1 area may play differential role in nociception of rats with a model of depression.

Behavioral effects of somatostatin microinjected into caudate putamen.

The present study examined the behavioral responses to bilateral microinjections of somatostatin (SRIF) into caudate putamen of male Wistar rats. SRIF locally administered at doses of 10, 50 and 100 ng/side dose-dependently affected locomotor activity, as reflected in both horizontal and vertical movements. SRIF modulated locomotor activity in a biphasic manner, exerting an inhibitory and a facilitatory effect. In the elevated plus-maze experiments, SRIF at doses of 50 and 100 ng/side microinjected bilaterally into caudate putamen decreased only the total number of entries in the open and closed maze arms, confirming the suppressing effect of SRIF on locomotion at the first 5 min.

Hippocampal asymmetry in exploratory behavior to vasoactive intestinal polypeptide

The effects of vasoactive intestinal polypeptide (VIP) microinjected uni- or bilaterally into the CA1 hippocampal area of male Wistar rats at a dose of 10, 50 and 100 ng on exploratory behavior were examined. VIP microinjected bilaterally at a high dose (100 ng) significantly decreased the horizontal movements, while at low doses (10 and 50 ng) had no effect on the exploratory activity. Microinjections of VIP into the left hippocampal CA1 area at doses 50 and 100 ng suppressed the exploratory activity, while right-side VIP administration at a dose 100 ng significantly increased horizontal movements compared to the respective controls. Vertical activity was stimulated only by VIP administered into the right hippocampal CA1 area at the three doses used. Neither bilateral nor left injections of VIP induced changes in the vertical movements. The main finding was the presence of hippocampal asymmetry in exploratory behavior to unilateral microinjections of VIP depending on the dose and the microinjected hemisphere.

Differential effects of somatostatin on exploratory behavior after unilateral injections into rat neostriatum

The effects of somatostatin (SRIF) microinjected unilaterally (left or right) at a dose of 10, 50, and 100 ng into the neostriatum of male Wistar rats on exploratory behavior were studied. Unilateral injections of SRIF suppressed dose-related the exploratory activity as decreased the number of horizontal and vertical movements compared to the respective controls. The effect was more pronounced when SRIF was microinjected into the right neostriatum as compared to the left neostriatum. These findings suggest some asymmetric effects of SRIF, depending on the dose and the microinjected hemisphere.

Lateralized learning and memory effects of vasoactive intestinal peptide infused into the rat hippocampal CA1 area

The effects of VIP microinjected unilaterally (left or right) and bilaterally (left and right) at a dose of 50 ng into hippocampal CA1 area of male Wistar rats on learning and memory (shuttle-box) were studied. Bilateral VIP microinjections impaired learning and memory, i.e., decreased the number of avoidances during the second training day and memory tests, compared to the respective controls. When infused into the left CA1 area, VIP exerted a marked inhibitory effect. Right-side VIP microinjections did not change the number of avoidances during the learning and memory tests. Compared to the right-side, left-side VIP infusions provoked a threefold decrease of the number of avoidances on the second training day and on the memory tests (24 h after the 2nd training day and on 7th day). These findings reveal lateralized inhibitory effects of VIP on cognitive processes in hippocampus.