Effect of clozapine on the behavioral and electrographic indices of the arrest function of the caudate nucleus in cats

In unrestrained cats clozapine in increasing doses (1--5 mg/kg) caused a behavioural depression and suppression of amphetamine-induced stereotypy of behaviour against the background of marked vegetative shifts. Similarly to chlorpromazine clozapine intensified the behavioural arrest reaction) and electrographic (neocortical caudate spindle) indices of the arrest function of the caudate nucleus. Arrest reaction changed more distinctly in stimulation of the ventral parts of the head of the nucleus. Clozapine also eliminated the weakening of the caudate responses caused by the stereotypical doses of amphetamine.     

Change in phenamine stereotypy in cats after the electrical stimulation of the caudate nucleus

Two types of behavioral shifts occur in cats after cessation of repeated low-frequency stimulation of the caudate nucleus head. Behavioral depression originates more frequently from the dorsomedial part of the head whereas stimulation of the ventrolateral part induces the activation before depression. The number and pattern of stereotype movements are variously changed against the background of these shifts following administration of the minimal effective phenamine dose. Desorganization takes place after stimulation of the dorso-medial nucleus parts followed by stereotypy reduction or, on the contrary, by its enhancement in combination with caudate activation.     

The effect of phenamine and caffeine on caudate inhibition of conditioned reflex avoidance reactions in cats]

In cats with a preliminarily learned conditioned avoidance reaction, stimulation of the caudate nucleus inhibited behavioral response by lengthening its latency and reducing the number of conditioned reactions. Intensity of the inhibitory effect did not substantially depend on the localization of electrodes in the head or body of the nucleus and weakened within a few experimental days. D,1-amphetamine (0.5 to 4 mg/kg) and caffeine (10 to 10 mg/kg) suppressed the caudate inhibition, but the action of the drugs was manifested in different ways. The influence of large doses of d,1-amphetamine was characterized by a serious disturbance of behaviour and caudate inhibition of conditioned responses.     

Stereotyped behaviour after cholinergic, but not dopaminergic, stimulation of the substantia nigra in rats

Stereotyped behaviour of the rat was measured after intracerebral drug application in an objective and quantitative way by means of a new method developed in this laboratory. Bilateral intranigral injection of apomorphine /APO/, a specific dopaminergic agonist, did not evoke any signs of stereotyped behaviour. Also ineffective was the application of APO in the amygdaloid nucleus. Dopaminergic blockade of the substantia nigra by topical application of triperidol, a potent dopaminergic antagonist, failed to influence the stereotypy elicited by systematic APO administrationDirect cholinergic stimulation of the substantia nigra with carbachol resulted in a dose-related stereotyped behaviour not distinguishable by sight from that evoked by systematic APO administration. The effect of intranigral carbachol was antagonized by a previous intraperitoneal injection of 10 mg/kg of atropine. Stereotypy could easily be produced also by intracaudate application of APO. Topical triperidol blockade of the caudate nucleaus prevented the stereotypy caused by intraperitoneal application of APO.It is concluded that at least a part of nigral neurons cannot be directly excited by apomorphine. However, they can be excited by carbacol and seem thus, to contain muscarinic receptors. The stimulation of these receptors results in an excitation of the neurons involved and produces marked stereotyped behaviour.     

Participation of the globus pallidus in the organization of stereotyped behavior in the cat

Electrical stimulation of the globus pallidus of cats produces a stereotype behaviour like that following the injection of high doses of d,1-amphetamine. This drug enhances pallidal response. On the other hand, pallidal stimulation facilitates formation of amphetamine-induced stereotypy which weakens after bilateral destruction of the globus pallidus. Neuroleptic haloperidol in very low doses abolishes pallidal as well as amphetamine-induced stereotypy. As supposed pallidal stereotypy may be connected with the disturbance of nigro-strio-pallidal relations.     

Behavioral and neurophysiological evidence for a facilatory interaction between co-existing transmitters: cholecystokinin and dopamine

Cholecystokinin (CCK) and dopamine (DA) co-exist in ventral tegmental neurons which project via the mesencephalic pathway to the nucleus accumbens of the rat. CCK and DA are located in separate neurons in the substantia nigra which projects via the nigrostriatal pathway to the caudate nucleus in the rat. The functional significance of this peptide-amine co-localization was investigated using behavioral and neurophysiological techniques. CCK injected directly into the nucleus accumbens potentiated apomorphine-induced stereotypy and dopamine-induced hyperlocomotion. CCK injected directly into the caudate nucleus had no effect on apomorphine-induced stereotypy or dopamine-induced hyperlocomotion CCK injected alone into either site did not induce stereotypy or hyperlocomotion. The dose-response curve to apomorphine induction of stereotypy was shifted to the left by CCK, indicating increased sensitivity to the dopaminergic agonist. Neurophysiological analysis of the firing rate of ventral tegmental neurons demonstrated that CCK produced a left-shift in the dose-response curve of apomorphine on inhibition of neuronal firing. These data suggest that CCK acts as a modulator of dopamine, increasing neuronal responses to dopaminergic agonists. The potentiation of dopamine by CCK may be specific to the mesolimbic neurons, where CCK and DA co-exist in the rat.     

Alterations in amphetamine stereotypy following acute lesions of substantia nigra

Stereotypy induced by high doses of amphetamine has been related to the ability of this drug to increase the release of dopamine in the caudate nucleus and to block its reuptake. Since amphetamine-stimulated dopamine release in the caudate is blocked by acute lesions of the nigrostriatal pathway, the mechanism by which amphetamine acts to produce stereotypy may be dependent upon intact nigrostriatal impulse flow. The present study examined the involvement of nigrostriatal impulse flow in amphetamine stereotypy by determining the effect of acute, bilateral lesions of substantia nigra pars compacta on measures of stimulant-induced stereotypy and motility. Acute nigral lesions did not significantly alter the stereotypy or motility induced by 3.0 or 6.0 mg/kg amphetamine. These results suggest that the observed behavioral effects of amphetamine do not require an intact nigrostriatal pathway, and thus may involve changes in spontaneous release or reuptake of dopamine rather than in changes in impulse-coupled dopamine release.     

EEG analysis of the effect of stimulation of GABAergic structures of the caudate nucleus on the development of the effect of haloperidol

Functional significance of GABA-structures of the caudate nucleus was studied by EEG analysis of the influence of stimulation of these structures on the development of the effect of systemic introduction of the blockader of dopaminergic receptors haloperidol. Microinjections of GABA to the caudate nucleus prevented the suppressing action of haloperidol on food-procuring cats behaviour and led to restoration of the EEG-reaction to conditioned sound stimuli. A conclusion is made about an important role of GABA-ergic structures in the mechanisms of dopaminergic control of the inhibitory function of the caudate nucleus.     

The effect of electrostimulation of the caudate nucleus and somatosensory cortex on defensive instrumental reactions in dogs]

It has been shown that the effect of stimulation of the caudate nucleus head in the contralateral hemisphere differs at different stages of achievement of a defensive instrumental habit in dogs. Stimulation preceding the action of the conditioned signal or delivered simultaneously with the beginning of the latter did not change the criteria for the achievement of successive programs of the instrumental defensive reaction. Stimulation of the same areas in the last phase of the instrumental response, as a rule, lead to the cessation of instrumental movement. A conclusion has been drawn that in a defensive situation the inhibitory influence of the caudate nucleus on instrumental behaviour of intact dogs is not so sharply expressed as in experiments with alimentary reinforcement. In dogs with a preliminary ablation of the CI and CII cortical zones of the contralateral hemisphere, stimulation of the caudate nucleus head was attended with a sharp drop in every criterion of the instrumental defensive reactions.     

Experimental stereotypy caused by disorders of GABA-ergic mechanisms in the caudate nuclei

The stereotypy was induced in rats by forming generators of pathologically intensified excitation (GPIE) on local disturbance of the inhibitory mechanisms in rostral portion of caudate nuclei, using bilateral injection of tetanus toxin. Microinjections of gamma-amino-butyric acid (GABA) into the area of the GPIE and systemic galoperidol administration inhibited the stereotypic behaviour of the animals. It is concluded that the formation of the GPIE may lie in the basis of stereotypy due to the disturbances in presynaptic link of the gamkergic system of caudate nuclei, dopaminergic neurons being an operant part of this GPIE.     

The effect of ablation of the caudate nucleus on the alimentary zone of the lateral hypothalamus]

A conditioned food-procuring reaction previously elaborated to an acoustic stimulus was reproduced in chronic experiments on six cats by means of direct electrical stimulation of the posterior parts of the lateral hypothalamus. Folloiwng extensive bilateral electrolytic ablation of the caudate nucleus, conditioned food-procuring reaction to the stimulation of the hypothalamus could not be reproduced for 40 to 70 days. The conditioned foor-procuring reflex to the acoustic stimulus disappeared for 14 to 30 days to be subsequently spontaneously restored. After caudatotomy, a diminution of the average amplitude of background oscillations and of evoked potentials to acoustic stimuli was recorced in the examined zones of the lateral hypothalamus. The part played by the caudate nucleus in the processes of alimentary behaviour activation is discussed.     

Neurophysiological analysis of postnatal development of corticostriate connections in rabbits

Evoked potentials were recorded in the caudate nucleus of adult rabbits and young rabbits aged 2–30 days in response to stimulation of the ipsilateral motor cortex. The response of the caudate nucleus in the adult rabbit consisted of a positive-negative complex with latent period of 3–5 msec. Maximal amplitude of the response was observed in the dorsorostral region of the nucleus. As the recording electrode was inserted deeper, the amplitude of the response gradually decreased but without reversal of its polarity. Responses of the caudate nucleus to stimulation of the motor cortex were recorded as early as on the 3rd day after birth. These responses were indistinguishable in configuration from responses of the nucleus of adult rabbits. Their latent period was about 10 msec. Between the 16th and 20th day after birth the latent period of the response decreased considerably — from 9 to 5 msec, and by the 30th day of life it had reached its definitive value. With age the amplitude of the response increased but the threshold of stimulation decreased, The results indicate early functional maturation of connections of the motor cortex with the caudate nucleus and they agree with the results of morphological investigations of the structural development of the afferent systems of this nucleus.Brain Institute, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 14, No. 3, pp. 284–289, May–June, 1982.     

电刺激大鼠尾核头部镇痛的中枢效应—[^3H]—2脱氧...

Sokoloff's 2-deoxyglucose (2-DG) autoradiographic technique was used to identify changes of glucose metabolic rate in the rat brain following unilateral stimulation of the head of the caudate nucleus. The results were as follows. The local glucose metabolic rate after noxious stimulation was increased in the somatosensory cortex, cingulate cortex, ventroposterior and parafascicular nucleus of the thalamus, septal area, habenular nucleus, head of caudate nucleus, periaqueductal gray (PAG) and dorsal raphe nucleus (P < 0.05). After stimulating the head of the caudate nucleus, the local glucose metabolic rate of nucleus raphe magnus (rm) and nucleus paragigantocellularis (pgcl) was increased significantly and that of the PAG and dorsal raphe nucleus had a tendency to increase, while stimulation of the head of caudate nucleus could partially abolish the increased glucose metabolic rate in the somatosensory cortex, cingulate cortex, ventroposterior and parafascicular nucleus of the thalamus, septal area and habenular nucleus as induced by noxious stimulation. These results suggest that caudate stimulation is able to depress the activation of some brain structures related to nociception and to activate those related to antinociception. The pgcl, rm, PAG and dorsal raphe nucleus might be the key structures participating in the caudate stimulation produced analgesia.     

Effect of catecholaminergic substances on the proconvulsive properties of the caudate nucleus]

In the freely moving rats stimulants of catecholaminergic tramission (DOPA, apomorphine, d,1-amphetamine, and also their combination with disulfiram) reduced the proconvulsive properties of the caudate nucleus. Under the effect of these substances there occurred a shortening of the cortical electroencephalographic response to a single stimulation of the nucleus in the animals given subconvulsive doses of pentaxylenetetrazol and a reduction of the extent of the spike-wave rhythm induced by the repeated caudate stimuli. On the contrary, inhibitors of catecholaminergic transmission (chlorpromazine, haloperidol, alpha-methyltyrosine and disulfiram) intensified the proconvulsive effect of the caudate nucleus.     

Effect of electric stimulation of the somatosensory cortex and caudate nucleus on extinctive inhibition of a conditioned alimentary reflex to sound]

In experiments performed on 9 dogs with alimentary method, extinctive inhibition was deepened and its elaboration was aceelerated by electrical stimulation of somatosensory and motor cortical areas and ventral segment of the caudate nucleus head. The extinction of the conditioned reflex was slowed down by stimulation of the anterolateral gyrus and the central segment of the caudate nucleus head. General motor excitation of animals during stimulation of the dorsal zone of caudate nucleus head impaired the elaboration of extinctive inhibition.     

Different role of various regions of the caudate nucleus in phenamine-induced stereotyped behavior in cats

Electrolytic ablation of the ventral parts of the cat caudate nucleus head results in an increase of frequency and disorganization of the pattern of the stereotype head turnings, induced by large doses of amphetamine. Lesion of the dorsal parts, on the other hand, is attended with a decreased number and limited manifestation of stereotype movements. A similar effect appears following a low frequency electrical stimulation of the nucleus ventral part. The disrupting action of neuroleptic haloperidol on the amphetamine-induced stereotype is weakened in animals with ventral lesions and enhanced in those with dorsal lesions. Due to dopaminergic activity, the amphetamine, apparently, produces a functional unbalance between different zones of the caudate nucleus, which underlies stereotype behaviour.     

Response of caudate nucleus neurons to acoustic stimulation during functional blockade of the thalamic centrum medianum in the cat

The response of caudate nucleus neurons to acoustic stimulation (a click at 0.5 Hz) was investigated during chronic experimentation in cats using intracellular techniques and reversible blockage of the thalamic centrum medianum produced by anode polarization. Having analyzed poststimulus histograms it was found that the response of phasic activation to an acoustic signal decreased, and disappeared in 52% of neurons. A reduction in the level of spontaneous activity was also observed in neurons of the caudate nucleus. The significance of a direct pathway from the thalamic centrum medianum to the caudate nucleus is discussed from the viewpoint of acoustic signal transmission to caudate nucleus neurons.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 18, No. 1, pp. 92–99, January–February, 1986.     

Formation of "caudate spindles" in the rabbit sensomotor cortex during ontogeny

Electrical activity of the sensomotor and visual areas of the neocortex during stimulation of the caudate nucleus was recorded in young rabbits aged 3–60 days and in adults. Single stimulation of the caudate nucleus was found to cause the appearance of characteristic bursts of spindle-like rhythmic activity ("caudate spindles"), described previously in cats and monkeys, in the adult rabbit cortex. The latent period of the caudate spindle was about 200 msec, its duration 1–3 sec, and the frequency of its oscillations of the order of 12 Hz. Caudate spindles were most marked in the sensomotor cortex of the ipsilateral hemisphere. In rabbits under 10 days old caudate spindles were not found even if the intensity of stimulation was increased many times. Starting from the age of 15 days bursts of rhythmic activity resembling caudate spindles, but with lower frequency (about 8 Hz), longer latent period (up to 350 msec), and also with a higher threshold, appeared in the sensomotor cortex. The definitive type of caudate spindles was established toward the end of the first month of postnatal life, corresponding to the time of formation and complication of conditioned-reflex activity in developing animals.Brain Institute, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 17, No. 1, pp. 11–15, March, 1985.     

Analysis of activity of neuron pairs in the cat caudate nucleus

Activity of neuron pairs in the caudate nucleus, derived simultaneously by a single microelectrode, was investigated in experiments on lightly anesthetized, immobilized cats. Strong temporal correlation was shown to be characteristic of the spontaneous activity of a neuron pair if grouped discharges were present in that activity. If, however, spontaneous activity was characterized by impulses randomly distributed in time, temporal correlation was observed in only 50% of cases, it was weaker, and it reflected excitatory and inhibitory interactions equally. In many cases negative correlation was observed in discharges of neurons within the time interval of 0–4 msec. Electrical stimulation of the various afferent inputs of the caudate nucleus not only did not cause correlation to appear in the discharges of the neurons but, on the contrary, it abolished correlation which existed for that same pair of neurons discharging spontaneously. Comparison of the results with data in the literature indicates that, by the character of interaction of its neurons, the caudate nucleus is one of the group of associative nuclei of the brain.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 10, No. 5, pp. 486–493, September–October, 1978.     

电刺激大鼠尾核头部镇痛的中枢效应——〔~3H〕-2脱氧葡萄糖放射自显影研究

本文利用[~3H]-2脱氧葡萄糖定量放射自显影方法,研究了电刺激大鼠尾核头部镇痛时中枢神经系统有关结构的葡萄糖代谢率变化。结果表明,痛刺激后,皮层躯体感觉Ⅰ,Ⅱ区、扣带回皮质、丘脑束旁核、丘脑中央中核、丘脑腹后核、尾核、外侧缰核、外侧隔核、中缝背核及中脑导水管周围灰质等结等的葡萄糖代谢率均明显升高(P<0.05)。电刺激大鼠尾核头部后,中缝大核及延髓旁巨细胞网状外侧核的葡萄糖代谢率显著升高,中脑导水管周围灰质和中缝背核的葡萄糖代谢率亦有升高趋势。电刺激大鼠尾核头部可部份降低痛刺激引起的有关结构葡萄糖代谢率升高(如皮层躯体感觉Ⅰ、Ⅱ区、扣带回皮质、丘脑束旁核、丘脑中央中核、丘脑腹后核、外侧隔核及外侧缰核等)。上述结果提示,电刺激大鼠尾核头部镇痛时抑制了与痛感觉有关的结构,同时激活了与镇痛有关的结构。中缝大核、中缝背核、中脑导水管周围灰质及延髓旁巨细胞网状外侧核等结构是实现尾核镇痛的重要环节。