Biomedical subjects

S M Brudzynski

Publications and source records attributed to S M Brudzynski.

At least 19 recordsLinked to original sources

PubMed1995

Mesolimbic dopamine terminals and locomotor activity induced from the subiculum.

The role of the mesolimbic dopamine terminals in the nucleus accumbens in the initiation of locomotion in rats was studied. Locomotor activity was initiated by activation of the excitatory input from the ventral subiculum to the nucleus accumbens with NMDA. Measurements of locomotor activity, induced by unilateral administration of NMDA into the ventral subiculum, were compared before and after destruction of the mesolimbic dopamine terminals in the nucleus accumbens. The dopamine terminals were destroyed by injection of 6-OHDA into the ventral tegmental area which projects to the nucleus accumbens. Injection of NMDA into the ventral subiculum caused an almost four-fold increase in locomotor activity. However, this increase was abolished after the destruction of the mesolimbic dopamine terminals in the nucleus accumbens. The results suggest that the mesolimbic dopamine terminals are essential in transmitting subicular signals to the output neurones within the nucleus accumbens.

Animals↗

PubMed1995

Behavioural responses of laboratory rats to playback of 22 kHz ultrasonic calls.

It has been demonstrated that cholinergic stimulation of the anterior hypothalamic-preoptic region induces 22 kHz ultrasonic vocalization in rats. Acoustic features of the cholinergically induced vocalization did not differ from those of 22 kHz calls emitted in natural situations and, therefore, could have a behavioural significance for other conspecifics. The 22 kHz calls induced by intracerebral injection of carbachol were played back to rats and their responses were compared with responses to playback of 22 kHz calls induced by tactile stimuli and to those with background noise. Animal responses were measured by an accelerometric sensor as an average ergometric activity. The average activity count was not changed during presentation of acoustic stimuli, however, striking differences were found in animal responses immediately after discontinuation of the sound. Activity of the rats consistently and significantly decreased after presentation of 22 kHz calls induced by tactile stimuli or by injection of carbachol. Animal responses to calls induced by carbachol were indistinguishable from responses to calls induced by tactile stimuli. No significant changes in the general activity of the animals were observed after presentation of the background noise or during the sessions without stimuli. The results demonstrate that carbachol-induced ultrasonic calls have behavioural significance for other conspecifics and could serve as an alarm call in a similar way to naturally produced 22 kHz vocalization.

Acoustic Stimulation↗

PubMed1995

Cholinergic mechanisms in generalized seizures: importance of the zona incerta.

OBJECTIVE: Stimulation of the central cholinergic system results in generalized epileptic seizures. The goal of this study was to map the epileptogenic effects of the cholinergic agonist, carbachol injected into different sites of the basal forebrain and diencephalon of the rat brain. METHODS: Carbachol was injected directly into the brain in a dose of 1 or 3 micrograms. Seizures were assessed behaviourally on a five-stage scale with electroencephalographic controls. Seizures at stage 1 were the least severe and those at stage 5 the most severe. RESULTS: Injections of high dose carbachol (3 micrograms) induced seizures from 40% of all injected brain sites. Injections of low dose carbachol (1 microgram) or isotonic saline into the same brain sites did not cause any behavioural or electrographic seizures. The majority of sites (84%) producing generalized seizures (stage 5) were concentrated in or around the zona incerta. CONCLUSIONS: Within the anatomical limits of the study, the zona incerta is the area most sensitive to carbachol-induced generalized seizures.

Animals↗

PubMed1995

Regional specificity of the emotional-aversive response induced by carbachol in the cat brain: a quantitative mapping study.

In this paper, the emotional-aversive response induced by intracerebral injection of carbachol has been studied in cats by recording their vocalization as an index of emotional behavior. The carbachol-induced responses were quantitatively mapped in the basal forebrain and diencephalic regions using the cumulative time of the animal's vocalization as a measure of response. The areas inducing the emotional- aversive response extended along two axes: 1. longitudinally along the neuraxis, from the reticular formation through the hypothalamus to the rostro-basal forebrain; and 2. vertically along the fornix, from the mediobasal hypothalamus to the septal area. The highest magnitude of the response (vocalization time) was obtained from a strip of tissue extending from the septum and preoptic area to the dorsal perifornical area, the dorsomedial hypothalamic nucleus, the paraventricular nucleus and the periventricular stratum. The pattern of distribution of reactive and nonreactive sites showed anatomic specificity, with the highest sensitivity found within the close periventricular tissue of the third ventricle. It is suggested that carbachol mapping selectively delineates the muscarinic cholinoceptive portion of the aversive, emotional brain system.

Animals↗

PubMed1994

Ultrasonic vocalization induced by intracerebral carbachol in rats: localization and a dose-response study.

It has been recently demonstrated that application of a cholinergic agonist, carbachol, into the anterior hypothalamic-preoptic area in the rat can induce 22 kHz ultrasonic vocalization. Functional mapping of the response in the forebrain and diencephalic regions of the rat brain, as well as the relationship between the dose of carbachol and the multi-parameter recording of vocalization are analyzed in the present study. Direct pressure injection of carbachol into the brain of adapted rats induced a 22 kHz ultrasonic vocalization from a limited region of the anterior hypothalamic-preoptic area and the vicinity of the septum. The response was antagonized by a local pretreatment with atropine and could not be induced by injections of saline vehicle or by handling. Measurements of summed duration of individual calls and response duration showed a typical dose-response relationship for 32-fold range of carbachol doses with ED50 = 0.73 micrograms (4.0 nmol). The increasing dosage of carbachol did not influence the frequency of emitted ultrasounds. On the other hand, the sound intensity increased and the bandwidth decreased with the increasing dosage of carbachol. The mean duration of single calls was also significantly decreased with the carbachol dosage. However, higher doses of carbachol decreased the number of short calls (100-150 ms) but increased the number of longer calls (300-400 ms). The duration of individual calls appeared to be a sensitive index of the response intensity. The results suggest that the cholinergic input into the mediobasal forebrain may play a physiological role in initiating and emitting the 22 kHz ultrasonic vocalization in rats, and that changes in call duration, intensity and bandwidth may be involved in conveying information for conspecifics.

Animals↗

PubMed1994

Involvement of M1 muscarinic receptors in the initiation of cholinergically induced epileptic seizures in the rat brain.

The present study was designed to determine the types of acetylcholine receptors involved in the initiation of epileptic seizures from the zona incerta and surrounding structures by cholinergic stimulation in rats. Unilateral intracerebral microinjection of the mixed muscarinic and nicotinic agonist carbachol (3 micrograms) produced generalized seizures in 12 of 20 rats studied. Local pretreatment with equimolar doses of acetylcholine receptor antagonists was used as a method of determining the receptor type involved in the initiation of cholinergically induced seizures in the rat diencephalon. Pretreatment with the M1 muscarinic receptor antagonist, pirenzepine (7 micrograms), abolished carbachol-induced seizures in 91% of the animals tested. The M2 muscarinic receptor antagonist, methoctramine (12 micrograms) and the nicotinic receptor antagonist, mecamylamine (3 micrograms), were relatively ineffective in antagonizing seizures in 9% and 27%, respectively. The results suggest that M1 muscarinic receptors are preferentially involved in the initiation of generalized epileptic seizures in the basal diencephalon of the rat.

Animals↗

PubMed1994

High-frequency ultrasonic vocalization induced by intracerebral glutamate in rats.

Direct injection of glutamate, a neuroexcitatory agent, into the anterior hypothalamic-preoptic area of the rat brain induced ultrasonic vocalization. This vocalization was characterized by short-duration calls (below 60 ms) of high sound frequency (pitch), mostly above 40 kHz, and was similar to the known 50-kHz vocalization observed in natural situations. The glutamate-induced vocalization was dose dependent within the dose range of 16.9-67.6 micrograms and was antagonized by local pretreatment with MK-801, an NMDA antagonist. The increasing dosage of glutamate induced more calls and had a significant influence on frequency and intensity of emitted ultrasound. The average sound frequency increased whereas the mean sound intensity decreased with the dosage of glutamate. On the other hand, the mean duration of a single call and the bandwidth did not significantly change with doses of glutamate. Injection of carbachol, a muscarinic cholinomimetic agent, into the same brain sites as glutamate, induced a different type of ultrasonic vocalization with low sound frequency and long call duration, known as 22-kHz calls. The results suggest that high sound frequency, short-duration calls (50 kHz) and low sound frequency, long-duration calls (22 kHz) have different neurophysiological and neurochemical mechanisms.

Animals↗

PubMed1994

Chromogranin A applied to the nucleus accumbens decreases locomotor activity induced by activation of the mesolimbic dopaminergic system in the rat.

The aim of the study was to obtain supporting evidence, using a behavioral paradigm, of the hypothesis that chromogranin A attenuates transmitter release in the CNS. We studied the effects of chromogranin A injected into the nucleus accumbens on locomotor activity triggered by application of picrotoxin into the ventral tegmental area of rats. Injection of picrotoxin into the ventral tegmental area, which is known to disinhibit dopaminergic mesolimbic neurons, caused a significant increase in horizontal activity. Distance covered during locomotion and movement time increased more than twofold, whereas stereotypy time and number, indices of nonlocomotor behavior, were not significantly affected by picrotoxin. Pressure injection of chromogranin A into the nucleus accumbens prior to injection of picrotoxin into the ventral tegmental area prevented these locomotor effects and had little or no effect on nonlocomotor behavior. Similarly, the picrotoxin-induced activity was prevented by injecting cobalt chloride into the nucleus accumbens. The results show that chromogranin A has an attenuating effect, either directly or indirectly, on dopaminergic neurotransmission in the nucleus accumbens that can be exemplified by inhibiting picrotoxin-induced locomotor activity. Further studies are needed to determine the mechanism of chromogranin A action in the nucleus accumbens.

Animals↗

PubMed1993

Analysis of 22 kHz ultrasonic vocalization in laboratory rats: long and short calls.

There is a remarkable variation in the length of single ultrasonic calls emitted by adult rats. The duration of calls is likely to convey information for conspecifics. The goal of the present study was to analyze 22 kHz calls emitted by naive laboratory rats in response to contact with the human hand and to measure their acoustic features, with a particular emphasis on call duration. Repeated hand touch applied to the nape of the neck of rats induced ultrasonic calls, 97.4% of which were within the range of 20-29 kHz and 2.6% of which were within 44-67 kHz. Distribution of duration of 6765 calls revealed two subpopulations of 22 kHz calls: 20-300 ms calls with its peak at 150 ms and calls above 310 ms with highest values at approximately 500-600 ms without a clear peak. These two call populations were referred to as short and long calls, respectively. The short and the long vocalizations contained 80% and 100% of calls within the range of the 22 kHz frequency, respectively. The findings indicated that, in the situation studied, the 22 kHz vocalization of adult rats consists of two distinguishable subpopulation of calls: short and long with the boundary between them at 300 ms.

Animal Communication↗

PubMed1993

Differential effects of quinpirole in the nucleus accumbens depending on the initial level of locomotor activity.

Effects of dopamine D1 and D2 receptor agonists (SKF 38393 and quinpirole, respectively) on locomotion were studied in two behavioural situations characterized by low and high level of exploratory locomotor activity. Administration of quinpirole bilaterally into the nucleus accumbens increased locomotor activity at the low initial level of activity and decreased locomotor activity at the high activity level, while the administration of SKF 38393 increased locomotor activity in both behavioural situations. It was concluded that quinpirole has differential effects on locomotion, depending on the initial level of activity.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1993

Emotional-aversive nature of the behavioral response induced by carbachol in cats.

Intrahypothalamic-preoptic application of carbachol induces a characteristic, emotional-aversive response in cats similar to their natural defensive behavior. This study was undertaken to provide quantitative evidence that the magnitude of the carbachol-induced, emotional-aversive response follows the same rules as natural responses to threat. An aversive emotional response can be described in terms of a spatiotemporal relationship between the animal and the relevant threat stimulus (potential danger). The physical distance to the threat stimulus and its movements should be predictive of the magnitude of the emotional response. The goal of the study was to test the relationship for the carbachol-induced response. The presentation of a threat stimulus (a human hand) to cats injected with carbachol caused a significant increase in vocalization. The magnitude of the response was inversely proportional to the physical distance between the cat and the threat stimulus. The hand in motion caused significantly longer vocalization than the immobile hand and cats not familiar with the experimental situation vocalized significantly more than those that had been exposed to the hand before. The spatiotemporal relationship between the animal and the threat stimulus strongly suggests that the carbachol-induced response is emotional and aversive in nature and does not differ from the relevant natural responses.

Animals↗

PubMed1992

Ultrasonic vocalization of laboratory rats in response to handling and touch.

The goal of the study was to investigate the ultrasonic vocalization induced in freely behaving, naive rats by gentle touch with a human hand. Thirty-nine rats were tested in an unfamiliar experimental cage with repeatable hand touch. Vocalization appeared with an average latency of 4.6 +/- 5.0 s (SD). The nape of the neck was the most effective area, and after a couple of stimuli applied, 66.7% of rats emitted 21-32 kHz ultrasonic vocalization. It consisted of multiple series of long calls, about 70% of which exceeded 300 ms. The responses quickly habituated from session to session to extinction. Significantly more rats housed in single cages vocalized ultrasonically than animals housed in community cages. The long latencies of the vocalization, their appearance in multiple series to a single touch, and quick habituation to the stimuli indicate that 22 kHz ultrasonic vocalization of rats reflects a distress caused by a potential danger to the animal and it does not necessarily reflect physical discomfort or pain. This vocalization may, therefore, play an adaptive role in increasing chances of survival by conveying information about potential threats to other conspecifics.

Animals↗

PubMed1991

Involvement of M1 and M2 muscarinic receptors of the basal forebrain in cholinergically mediated changes in the rat locomotion.

1. Wistar rats were implanted with cannulae into the medial preoptic and anterior hypothalamic areas for intracerebral injections. 2. Unilateral intracerebral injections of carbachol (1 microgram) into a limited area of the basal forebrain decreased significantly both the distance travelled by the animals and time spent walking. 3. In addition to the decrease in locomotion, it was demonstrated for the first time that injections of carbachol also slow animal movement by significantly decreasing speed of forward progression. 4. All locomotor effects of carbachol were reversed by local pretreatment with atropine (1 microgram) but not by pirenzepine (2 micrograms) suggesting that these effects were mediated by M2 muscarinic receptors with minimal or no M1 receptor involvement.

Animals↗

PubMed1991

Response of neurons of the rat anterior hypothalamic-preoptic area to carbachol.

Behavioural effects of carbachol given into the hypothalamic/preoptic area have been demonstrated but there is a paucity of information about the response of single neurons to carbachol. The aim of the present study was to determine the response of spontaneously firing neurons in the rat hypothalamic/preoptic area to application of carbachol by iontophoresis or by pressure injection in a dose and volume comparable with that used in behavioural studies. Extracellular single unit recordings showed a significant decrease in mean firing rate in 82% of neurons responding to iontophoretic carbachol and in 75.5% of neurons responding to carbachol injected about 600 microns away. An increase in firing rate occurred in only 15 and 17.6% of neurons, respectively. Application of saline did not alter the mean firing rate while application of glutamate into the same areas or ejection into the vicinity of the same neurons caused an increase in mean firing rate in 94% of responding neurons. The results indicate that a decrease in mean firing rate is the predominant neuronal response to carbachol in the anteromedial hypothalamic/preoptic area of the rat and we suggest that this decrease may be associated with behavioural responses to carbachol.

Animals↗

PubMed1991

Comparison between cholinergically and naturally induced ultrasonic vocalization in the rat.

Ultrasonic vocalization in rats accompanying stressful situations or induced by direct brain stimulation may be used as a measure of emotionality and as a potential response model for testing anti-anxiety agents. The aim of the present study was to compare physical features of pharmacologically-induced ultrasonic vocalization with naturally triggered vocalization. Ultrasonic calls induced by hand touch, footshock, or by direct intracerebral injection of carbachol in adult rats were compared. Ultrasonic calls obtained in all these situations were described as '22 kHz' vocalization. Average frequencies of vocalization were 24.1 +/- 0.78 kHz, 26.0 +/- 2.64 kHz and 25.0 +/- 1.87 (SD) kHz for handled, footshocked and carbachol injected rats, respectively, and they did not differ significantly from each other. Histograms of single call duration showed similar distribution patterns for all groups with a predominance of long calls, although carbachol-induced calls were shorter than calls induced by touch or footshock. Histograms for inter-call intervals showed one major peak at 100-150 ms for all groups. Sonograms and power spectra showed similar characteristics both for calls induced by intracerebral carbachol and by hand touch or footshock. The results indicate that physical features of ultrasonic vocalization induced by intracerebral carbachol are comparable with those for naturally induced vocalization and fall into the category of '22 kHz' calls.

Animals↗

PubMed1990

Ultrasonic vocalization in rats produced by cholinergic stimulation of the brain.

Neurotransmitters involved in production of ultrasounds in rodents have not yet been identified. It is also not known whether brain mechanisms regulating production of ultrasounds and audible sounds are similar or different. The present study provides the first report that intracerebral injection of an acetylcholine agonist, carbachol, in rats induces ultrasonic vocalization. Since the same agent can induce audible vocalization in cats, the finding suggests a possible common neurochemical substrate underlying production of sonic and ultrasonic vocalization in mammals. The data accumulated to date indicate also that these two kinds of vocalization may play a homologous role in animal communication.

Animals↗

PubMed1990

Evidence for involvement of endogenous acetylcholine in emotional-aversive response in the cat.

1. The purpose of the present study was to provide evidence for involvement of endogenous acetylcholine in naturally as well as pharmacologically induced emotional behaviour in the cat. 2. Emotional-aversive responses of 10 cats were naturally evoked by presentation of a dog or the responses were pharmacologically induced by intracerebral injections of cholinomimetics. 3. Naturally evoked emotional behaviour was abolished by i.p. pretreatment with atropine sulfate (1 mg/kg), but not by atropine methyl nitrate, or it was significantly decreased by bilateral intracerebral injection of atropine sulfate (5 micrograms/microliter). 4. On the other hand, intracerebral injections of physostigmine (100 micrograms/microliter), an acetylcholinesterase inhibitor which elevates the level of endogenous acetylcholine, induced the fully developed emotional-aversive response comparable with natural behaviour and with responses induced by carbachol (10 micrograms/microliter). 5. The results demonstrate that the endogenous acetylcholine in the basal forebrain and diencephalic areas play a role in naturally occurring emotional aversive behaviour in cats.

Acetylcholine↗

PubMed1989

Cholinergically mediated reduction of locomotor activity from the basal forebrain of the rat.

Carbachol when injected into the basal forebrain alters spontaneous motor behavior and usually decreases locomotion. However, the extent of the brain area producing this effect has not yet been determined. The goal of the present study was to use quantitative mapping of injection sites to further localize the effect of carbachol on spontaneous locomotion of rats. The distance travelled by an animal and the time spent moving were simultaneously measured before and after injection of carbachol or saline into 96 sites in the basal forebrain. Each site was injected with 1.0 microgram (5.47 nmol) of carbachol, a dose close to ED50, in a volume of 0.2 microliter. A decrease in spontaneous locomotion was obtained as a result of injections of carbachol into the preoptic and anterior hypothalamic areas, particularly into the medial preoptic nucleus and the latero-anterior hypothalamic nucleus. The area from which a consistent decrease in spontaneous locomotion was obtained was surrounded by an area producing an increase in locomotion with a narrow zone of overlap. This decrease in locomotion was dose dependent and reversed by atropine. The results indicate that both the decreasing and increasing effects of carbachol on locomotion are anatomically specific and that the decreasing effects can be elicited from a limited forebrain area. It is suggested that muscarinic cholinergic mechanisms in the basal forebrain may be involved in the pathogenesis of neural dysfunction associated with locomotor activity in man.

Animals↗