[The effects of selective 5HT3 receptor blockade on physiological markers of abdominal pain in awake dogs].

In awake dogs, the visceromotor and cardioautonomic responses to the rectal balloon distension were studied before and after intravenous administration of a selective 5HT3 receptor antagonist granisetron. It was shown that balloon distension level up to 60 mmHg caused neither noticeable muscle responses nor substantial changes in heart rate. In turn, distending pressures of 80 mmHg and higher induced vigorous abdominal muscle contractions and tachycardia that were graded with increasing intensities of stimulation. Thus, the rectal stimulation with pressures 80 mmHg and more produced the changes in visceromotor and cardiovascular indices which could be considered as suitable indicators of visceral nociception in conscious animals. Based on monitoring of these physiological markers in a model of abdominal pain the dose-dependent antinociceptive effect of granisetron in awake dogs has been demonstrated for the first time. It was determined that granisetron in doses of 0.25, 0.5 or 1.0 mg/kg induced correspondingly 33.6 +/- 9.2, 58.0+/- 8.6 [see text] 76.7 +/- 5.5 % decrease in visceromotor response of dogs to nociceptive visceral stimulation. The effect occurred immediately after the drug administration and was lasting more than 90 min. In turn, the dose-dependent suppression of the rectal distension-induced tachycardia was less prominent and only observed during the initial period of granisetron action. The described model of abdominal pain in awake dogs might be useful for preclinical screening of new pharmacological substances, whereas the obtained data could contribute to the development of more efficient analgesics aimed in patients with irritable bowel syndrome.

[Effect of migrepin on activity of trigeminal nucleus caudalis neurons].

Neurophysiological experiments on anesthetized rats were used to study the effects of various doses (12.5, 25, 37.5 mg/kg, i.v.) of drug composition migrepin (representing a combination of potassium-2,4-dichlorobenzoate, carbamazepine, and caffeine) on background firing of the trigeminal nucleus caudalis neurons and their responses to electrical stimulation of the dura mater. It was found that migrepin produces direct, dose-dependent inhibitory action on functional activity of TNC neurons. The results confirmed anti-migraine properties of the drug but did not exclude the necessity to study its action in clinical trials.

[Responses of neurons of the solitary tract nucleus to noxious colorectal distension in rats].

In experiments on anaesthetized rats, the neuronal mechanisms underlying processing of the nociceptive information from the colon within the nucleus of the solitary tract were studied. In addition, the role of nitric oxide in these processes was estimated. Analysis of changes in c-fos expression revealed that nociceptive colorectal distension (CRD) resulted in activation of neurons mainly in the medial, commissural, parvicellular and dorsomedial subnuclei of the solitary tract nucleus. Non-noxious CRD evoked in these subdivisions weak phasic excitatory neuronal responses. Under noxious CRD, neurons with phasic (58%) and tonic (42%) responses were revealed. The phasic neuron responses were significantly enhanced in comparison with non-noxious CRD. Inhibition of the neuronal NO-syntheses resulted in significant decrease of neuron responses to noxious CRD and the number of cells with tonic reactions. Therefore, neurons with tonic responses may be directly related to NO-depended processing ofnociceptive information from colon.

[Effects of the insular cortex stimulation upon realization of the antro-fundal gastric reflex in alert dogs].

Neuroanatomic studies demonstrate direct descending projections from the insular cortex to the gastric area of the solitary tract nucleus. This allows us to hypothesize that the insular cortex is able to modulate vago-vagal gastric motor reflexes such as antro-fundal inhibitory reflex. In experiments on conscious dogs demonstrating fasting gastric motility, the effects of electrical stimulation of the insular cortex upon realization of the gastric antro-fundal reflex were studied. Distension of the antrum applied during active period of gastric motility inhibited contractions of the fundus. Electrical stimulation of the insular cortex did not affect the time pattern of fasting gastric motility but resulted in significant prolongation of the antro-fundal reflex. Thus, activation of the insular cortex leads to augmentation of gastric vago-vagal inhibitory reflex. The effect may be realized due to corticofugal modulation ofvago-vagal neurotransmission within the nucleus of the solitary tract.

[Localization of the neurons of the amygdala central nucleus projecting to the hypothalamic paraventricular nucleus area].

The aim of this study was to identify, using retrograde axonal transport of horseradish peroxidase in rats, the cells, within distinct divisions of the amygdala central nucleus, innervating hypothalamic paraventricular nucleus area. The labeled cells were found in the ipsilateral amygdala central nucleus in the whole of its rostro-caudal extension. The maximal number of labeled neurons was detected in the middle third of the nucleus, corresponding to the intermediate subnucleus of the central nucleus. Single cells were located in the medial and the lateral subnuclei of the amygdala central nucleus. Labeled neurons of the intermediate subnucleus were represented by the oval cells or the cells of an indefinite form.

[NO-dependent mechanisms of the amygdalofugal modulation of the hypothalamus vegetative neurons].

In neurophysiological and histochemical experiments on rats, amygdalo-fugal modulation of cells within NO-producing areas of the hypothalamus was studied. Electrical stimulation of the medial area of the central nucleus caused obvious excitatory neuronal reactions within the medial part of the paraventricular nucleus and rostral portion of the lateral hypothalamic area. The observed amygdala-induced neuronal responses were enhanced after i.v. N-nitro-1-arginine methyl ester (L-NAME, 10 mg/kg). The nistochemical study revealed that the central nucleus stimulation caused an increase in number and optical density of the NADPH-d-positive cells within the parvicellular zone of the paraventricular nucleus and in the medial part of the lateral hypothalamic area. The NO-producing cells within the ventrolateral part of the lateral hypothalamic area were inhibited. The described phenomenon may underlie the amygdalo-fugae modulation of autonomic outflow.

[Possible mechanisms of amygdala participation in the regulation of gastric motor activity]. / Vozmozhnye mekhanizmy uchastiia mindalevidnogo kompleksa v reguliatsii motornoi funktsii zheludka.

Mechanisms of the amygdala central nucleus (CNA) influence on gastric motor reflex activity were studied in electrophysiological and neuroanatomical experiments in Wistar rats. In the anaesthetized animals, electrical stimulation of the CNA affected spontaneous gastric motility and caused inhibitory as well as excitatory changes of vagus-induced gastric relaxation. The most significant and mainly inhibitory effects were observed under the stimulation of the medial CNA. Microinjection of the anterograde tracer Phaseolus vulgaris-leucoagglutimn (PHA-L) into the different divisions of the CNA revealed direct projections from its dorso-medial portion to the gastric related area of the dorsal vagal complex. Electrical stimulation of this amygdaloid area was found to change activity of the bulbar gastric related neurons. Inhibitory and excitatory changes of their vagus-induced responses under the amigdala stimulation were manifested as a general modulation of all phases of the reaction or a selective modulation of some of them. These mechanisms may underlie the amygdalo-fugal modulation of gastric motor reflex activity.

Amygdalofugal modulation of the vago-vagal gastric motor reflex in rat.

In experiments on urethane anaesthetized rats the influence of electrical stimulation of the central nucleus of the amygdala (CNA) on gastric motility and activity of gastric-related neurons of the dorsal vagal complex was studied. Stimulation of the CNA effected spontaneous gastric motility and caused both excitatory and inhibitory changes of vagal-induced gastric relaxation. The most significant effects, mainly inhibitory, were observed under stimulation of the medial CNA. This amygdaloid area was found to influence activity of gastric-related neurons of the dorsal vagal complex. Excitatory and inhibitory changes of their vagal-induced responses under the amygdala stimulation manifested as general modulation of all phases of the reaction or selective modulation of some of them. These mechanisms may lie at the base of amygdalofugal modulation of gastric reflex activity.

Projections from the central nucleus of the amygdala to the gastric related area of the dorsal vagal complex: a Phaseolus vulgaris-leucoagglutinin study in rat.

Electrophysiological and anatomic studies suggest that the amygdala regulates gastrointestinal motility and gastric acid secretion via projections to the dorsal vagal complex. The topography of these projections is poorly understood. Here, these projections were investigated by injecting anterograde tracer, Phaseolus vulgaris-leucoagglutinin, into the different divisions of the central nucleus of the amygdala in 13 rats. The distribution of immunohistochemically labeled terminals in the different portions of the dorsal vagal complex was analyzed. We found that (1) the dorsal aspect of the medial division of the central nucleus provided moderate projections to the dorsal vagal complex; (2) the heaviest projections terminated in the parvicellular and medial divisions of the nucleus of the solitary tract. These data suggest that via topographically organized projections, the amygdala can modulate the vago-vagal gastrointestinal reflexes in emotional and stressful situations.

[The neurons of the medial vestibular nucleus initiating the relaxation of the rat's stomach wall]. / Neirony medial'nogo vestibuliarnogo iadra, initsiiruiushchie relaksatsiiu stenki zheludka u krys.

In acute rat experiments the technique of retrograde axonal transport of horseradish peroxidase in the medial vestibular nucleus allowed to identify a group of neurones sending axons to the "stomach" region of a single tract nucleus. These neurones and, accordingly, the descending vestibular/solitary links can be viewed as the morphologic basis for vestibular influences on the gastric motor activity. As was shown, local irritation of the neurones initiates relaxation of the stomach wall. Activation of the anterior limbic cortex modulates the vestibular/autonomous responses of the intragastric pressure reduction. Irritation of the infralimbic cortex of the rat's brain may have a preventive effect on the stomach wall relaxation stimulated by the vestibular neurones projecting on the "stomach" region of single tract nucleus.

[Possible mechanisms of the anterior limbic cortex influence on the neuron activity of the vago-solitary complex]. / Analiz vozmozhnykh mekhanizmov limbicheskoi kory na aktivnost' neironov vago-solitarnogo kompleksa.

In ananesthetized cats, neurons of the nucleus of the tractus solitarius (NTS) and the dorsal motor nucleus of the vagus nerve (DMNV) revealed phasic excitatory responses to separate single vagal and cortical stimuli. Stimulation of the anterior limbic cortex combined with vagal stimulation resulted in inhibitory or excitatory modification of the vagal induced responses of the NTS and DMNV neurons. The data obtained suggest that complete inhibitory effects are related to general cortical mechanisms of control of the functional state of the brain stem visceral neurons. Selective inhibition of the vagal induced responses by limbic cortex stimulation is due to particular cortical mechanisms of the visceral sensory transmission control via the NTS neurons.