Motor effects of electrical and cholinergic stimulation of the cat's dorsal hippocampus

The effect of electrical stimulation of the dorsal hippocampus was studied in 17 adult cats with implanted electrodes and those effects of carbachol and dioxolane in a group of ten adult cats with a cannula and electrodes implanted in the above cited structure. Electrical stimulation induced a contralateral head-eye-body turning response in 3 cats (17.6%), only when it was associated with afterdischarge. On the other hand the cholinergic agonists evoked contralateral head-eye-body turning in nine out of ten cats in whom the injections were administered into the hippocampus. The fact that dioxolane, an exclusive muscarinic agonist evoked this behavior and that atropine sulfate blocked this response, favours the postulation that turning is due to activation of muscarinic receptors inside the dorsal hippocampus. Comparison was done between the hippocampal group with a group similarly studied with electrodes implanted in the pulvinar-lateralis posterior nucleus complex (P-LP), and in the caudate nucleus, in which the electrical stimulation evoked contralateral head-eye-body turning response without any EEG activation.     

Serotonergic mechanisms of the lateral parabrachial nucleus and cholinergic-induced sodium appetite

Central cholinergic mechanisms are suggested to participate in osmoreceptor-induced water intake. Therefore, central injections of the cholinergic agonist carbachol usually produce water intake (i.e., thirst) and are ineffective in inducing the intake of hypertonic saline solutions (i.e., the operational definition of sodium appetite). Recent studies have indicated that bilateral injections of the serotonin receptor antagonist methysergide into the lateral parabrachial nucleus (LPBN) markedly increases salt intake in models involving the activation of the renin-angiotensin system or mineralocorticoid hormones. The present studies investigated whether sodium appetite could be induced by central cholinergic activation with carbachol (an experimental condition where only water is typically ingested) after the blockade of LPBN serotonergic mechanisms with methysergide treatment in rats. When administered intracerebroventricularly in combination with injections of vehicle into both LPBN, carbachol (4 nmol) caused water drinking but insignificant intake of hypertonic saline. In contrast, after bilateral LPBN injections of methysergide (4 microg), intracerebroventricular carbachol induced the intake of 0.3 M NaCl. Water intake stimulated by intracerebroventricular carbachol was not changed by LPBN methysergide injections. The results indicate that central cholinergic activation can induce marked intake of hypertonic NaCl if the inhibitory serotonergic mechanisms of the LPBN are attenuated.     

The metabolism of dopamine in rat caudate nucleus can be increased by in vivo “dialysis” perfusion cannulae

The development of dialysis cannula techniques coupled with high performance liquid chromatography and electrochemical detection (HPLC-EC) has provided a means to continuously sample extracellular fluid from deep brain structures $\text{in vivo}$. The present studies show that with HPLC-EC analysis of the acid metabolites of dopamine (DA) and 5-hydroxytryptamine (5-HT) in samples from dialysis cannulae implanted in the caudate nucleus of anaesthetized rats, it is possible to determine the time course of the response of dopamine- and 5-HT containing neurones to administration of monoamine oxidase inhibitors and haloperidol. The tissue concentrations of the DA and 5-HT metabolites were also determined at the conclusion of each individual experiment in both the caudate nucleus containing a cannula and in that without a cannula. In perfusion experiments where no drug was administered the content of the DA metabolites, but not that of the 5-HT metabolite, were significantly elevated in the caudate nucleus containing the cannula as compared with the contralateral tissue. These increases occurred whether the cannula was perfused or not, suggesting that the presence of the cannula may have been causing a lesion which altered the activity of the DA neurones. These results emphasize the importance of tissue analysis in conjunction with the dialysis experiments, especially where perfusion sample contents of the monoamine metabolites are being measured as a reflection of the effects of behavioural manipulation or drug treatment on endogenous neuronal activity.     

Alpha-MSH injected into the substantia nigra or intraventricularly alters behavior and the striatal dopaminergic activity

Rats were injected with 1 μg of alpha-melanocyte stimulating hormone (α-MSH) into the third ventricle and locally in the ventral tegmental area and in different regions of the substantia nigra. The modifications produced on grooming behavior and locomotion as well as on the dopamine content of the nucleus accumbens and the caudate putamen, were studied. Both intraventricular peptide administration and microinjections into the ventral tegmental area induced excessive grooming and a significant increase of the locomotor activity. The dopamine content of the nucleus accumbens and caudate putamen was markedly reduced. Injections of the peptide into the substantia nigra pars compacta failed to induce excessive grooming but did provoke a slight increase in locomotor activity and a smaller change in caudate dopamine content than that observed by injections in the ventral tegmental area or in the third ventricle. Dopamine levels in the nucleus accumbens were not changed. Finally, the injections of α-MSH into the lateral substantia nigra did not produce either biochemical or behavioral changes.The results suggests that α-MSH can modify, directly or indirectly, the striatal dopaminergic activity and that the behavioral alterations observed such as excessive grooming, could be mediated by the activation of the dopamine cells from the ventral tegmental area, that in turn may provoke a significative release of dopamine at the caudate putamen nucleus as well as in nucleus accumbens.     

In vivo release of adenosine from cat basal ganglia—studies with a push pull cannula

The release of newly synthesized [³H]adenosine has been studied in vivo in cat caudate nucleus and substantia nigra, using a push pull cannula. In the presence of [³H]adenosine as precursor, spontaneously released [³H]adenosine was easily detectable in superfusates of the push pull cannula. In the caudate nucleus, potassium and veratridine caused a marked and reversible increase in [³H]adenosine release. The effect of veratridine was completely blocked by tetrodotoxin (TTX) although TTX had no action by itself. Ouabain as well as glutamate, also markedly increased the release of [³H]adenosine.The specific 5′ nucleotidase inhibitor α,β-methylene ADP, did not alter the increase in the amount of [³H]adenosine obtained by veratridine, although it diminished the spontaneous release of [³H]adenosine by about 20%.Push pull cannulae were also implanted simultaneously into the caudate nucleus and substantia nigra. Potassium applied into the caudate nucleus increased the local release of adenosine but did not change that observed in the substantia nigra. When potassium was applied into the substantia nigra, it also increased the local release of adenosine but did not change that observed in the caudate nucleus.The results are discussed in term of the possible existence of “purinergic neurons” and of the relation between the adenosine release and central nervous activity.     

Effects of Single and Repeated Electroconvulsive Shock Administration on Inositol Phosphate Accumulation in Rat Brain Slices

Accumulation of inositol-1-phosphate after labeling with [3H]inositol and stimulation with noradrenaline, carbachol, and serotonin was measured in rat cortical, caudate nucleus, and hippocampal slices. The response to noradrenaline was significantly increased in cortical slices from animals that had received either a single electroconvulsive shock (ECS) or a series of 10 daily ECS but was unchanged in caudate nucleus or hippocampal slices. The response to carbachol, a muscarinic cholinergic agonist, was unchanged in cortical or caudate nucleus slices but was significantly reduced in hippocampal slices from animals that had received chronic ECS. The response to serotonin in cortical slices was not affected by the treatment. The results are correlated with changes in receptor number, which have been demonstrated to occur after administration of ECS.     

Tremor following intracerebral carbachol injection. 1.Carbachol sensitivity of various brain structures]

Tremor produced by intracerebral injection of carbachol. I. Susceptibility of different brain areas to carbachol Microinjections of carbachol into the lateral ventricle of rats caused tremor depending on dose. Intensity and duration of motor effects after injection of carbachol (30 mug/3 mul bilateral) into different brain areas were found to depend on localization: strongest tremor was elicited by injections into the nucleus caudatoputamen and cortex cerebri, moderate tremor by administration into the substantia nigra reticularis, globus pallidus and thalamic brain regions. Target areas of mean sensitivity were demonstrated in more rostral and caudal parts of the formatio reticularis. The injection of carbachol into the nucleus ruber, nucleus linearis and substantia nigra compacta brought about lowest tremor values. Ablation of the site of injection from the remaining brain abolished tremor induced by carbachol contrary to the tremor induced by oxotremorine.     

清醒大鼠室旁核微量注射心房钠尿肽对压力感受性反射敏感性的影响

心房钠尿肽(atriaI natriuretic peptide,ANP)作为一种神经递质或调质可能参与心血管活动的中枢调节。本实验在清醒大鼠室旁核(paraventricular nucleus,PVN)注射ANP,探讨其对压力感受性反射敏感性的影响,并通过侧脑室注射血管升压素受体Ⅰ阻断剂OPC-21268,观察ANP对压力感受性反射敏感性的调节是否与中枢血管升压素有关。实验中观察到,在PVN内微量注射ANP(6、60 ng/0.2μl)可明显提高压力感受性反射敏感性(P<0.05),侧脑室预先注射OPC-21268 (0,45 μg/3 μl)后,ANP对压力感受性反射敏感性的增强作用明显减弱(P<0.05)。静脉注射ANP(60 ng/0.04 ml)不影响压力感受性反射敏感性。上述结果提示,心房钠尿肽对压力感受性反射活动起易化作用,心房钠尿肽的这种中枢作用可能部分通过中枢血管升压素介导。     

Is cholinergic activity of the caudate nucleus involved in memory?

A review was made of experiments dealing with the involvement of cholinergic activity of the caudate nucleus in memory processes. Injections of acetylcholine-receptor blockers or of neurotoxins against cholinergic interneurons into the striatum produce marked impairments in acquisition and retention of instrumental tasks while injections of acetylcholine or choline into the caudate produce the opposite effect. However, after a period of overtraining cholinergic blockade or interference with neural activity of the caudate does not produce significant deficits in retention. It is concluded that striatal cholinergic activity is critically involved in memory of recent events and that long-term memory is mediated by different neurochemical systems outside the caudate nucleus.     

A Search for Receptors Modulating the Release of γ-[3H]Aminobutyric Acid in Rabbit Caudate Nucleus Slices

Various putative striatal transmitters and related compounds were studied for their effects on the release of gamma-aminobutyric acid (GABA) from slices of the head of the rabbit caudate nucleus. The slices were preincubated with [3H]GABA and then superfused and stimulated electrically at 5 or 20 Hz. Aminooxyacetic acid was present throughout. The main changes observed were the following. The basal and, less consistently, the electrically evoked overflow of [3H]GABA were enhanced by 3,4-dihydroxyphenylethylamine (dopamine), an effect not blocked by cis-flupentixol or domperidone and not mimicked by apomorphine and D1-selective agonists. The electrically evoked overflow was diminished by 5-hydroxytryptamine (serotonin); the inhibition was prevented by methiothepin. The basal but not the electrically evoked overflow was enhanced by carbachol; acetylcholine and nicotine also accelerated the basal outflow whereas oxotremorine caused no consistent change; the effect of carbachol and acetylcholine were blocked by hexamethonium but not by atropine or by tetrodotoxin. These findings indicate that the GABA neurons in the caudate nucleus may be stimulated by dopamine, although the receptor type involved remains unclear; inhibited by serotonin; and stimulated by acetylcholine acting via a nicotine receptor. However, all drug effects observed were relatively small. No evidence was obtained for autoreceptors, alpha 2-adrenoceptors or receptors for opioids, adenosine or substance P at the GABA neurons.     

Cholinergic effect on the dopamine turnover in the rat corpus striatum]

The peripheral administration of oxotremorine caused a significant increase in dihydroxyphenylacetic acid (DOPAC) in the striatum of rats, dopamine (DA) level was unaffected. Injection of oxotremorine into the substantia nigra failed to change the content of dopamine and its acid metabolites homovanillic acid (HVA) and DOPAC in striatum. Injection of oxotremorine or carbachol into the substantia nigra or into the caudate nucleus did not significantly influence the DA-turnover. The partly inconsistent results are discussed in connection with literature data in regard to the existence of excitatory as well as inhibitory cholinergic systems, which are located differently and are involved in the regulation of DA-turnover.     

Muscarinic cholinergic receptor blockade impairs free fatty acid mobilization during fasting in pigeons (<Emphasis Type="Italic">Columba livia</Emphasis>)

The effects of intracerebroventricular pretreatment with muscarinic (scopolamine or methylscopolamine; 2.7 nmol or 5.4 nmol) or nicotinic (mecamylamine, 2.7 nmol or 5.4 nmol) cholinergic receptor antagonists on plasma free fatty acid increases induced by intracerebroventricular injections of carbachol in conscious resting pigeons (Columba livia) were examined. Plasma glucose levels were also measured throughout the experiments. Pretreatment with methylscopolamine suppressed the lipolytic effect of carbachol injections, while mecamylamine left this response unchanged. Neither carbachol treatment alone, nor the pretreatments with cholinergic agents affected glucose levels. Subsequently, the effects of intracerebroventricular injections of methylscopolamine were investigated in 24-h food-deprived pigeons. The increase in free fatty acid levels after fasting was of a magnitude similar to that observed after carbachol treatment; intracerebroventricular injections of methylscopolamine (5.4 nmol) transiently but powerfully decreased plasma free fatty acids in 24-h food-deprived pigeons to levels comparable to those of free-feeding animals. The fasting-induced decrease in glucose levels was not affected by this treatment. These data indicate that the lipolytic response induced by carbachol may be mediated by central muscarinic cholinergic receptors and that this central cholinergic mechanism partially contributes to plasma free fatty acid increases observed during fasting. Furthermore, the absence of effects on glucose levels suggests that these cholinergic mechanisms participate selectively in the lipolytic component of the metabolic response to fasting.     

氨甲酰胆碱引起的促钠排泄与下丘脑TH—IR神经元活性的变化

目的：我们最近的实验发现大鼠侧脑室注射氨甲酰胆碱引起显著的促钠排泄作用,本工作同时还观察了下丘脑内不同脑区的儿茶酚胺能神经元活性的变化。方法和结果：氨甲酰胆碱注射后４０ｍｉｎ,下丘脑室旁核的腹侧和内侧小细胞部、内侧视前区、尾核、苍白球的酪氨酸羟化酶免疫反应（ｔｈｙｒｏｓｉｎｅｈｙｄｒｏｘｙｌａｓｅｉｍｍｕｎｏｒｅａｃｔｉｖｉｔｙ,ＴＨＩＲ）阳性细胞数减少,免疫反应染色强度降低;下丘脑室旁核的后部,下丘脑前区的后部、下丘脑室周核、弓状核、下丘脑外侧区的ＴＨＩＲ阳性细胞数增多,免疫反应染色强度增强。结论：侧脑室注射氨甲酰胆碱对脑内不同脑区的内源性儿茶酚胺能神经元分别有兴奋或抑制作用,其与促钠排泄的关系将在本文中讨论     

Role of acetylcholinergic structures of the caudate nucleus in mechanisms of inhibition of a conditioned food-getting reflex in the cat

The effect of acetylcholinergic structures stimulation on the acquisition and inhibition of a conditioned food-procuring reflex was studied in cats. Physostigmine injections (0.1 mg/kg) did not facilitate the extinction of the non-reinforced food-procuring reactions of caudatectomized cats in contrast to the intact or lobectomized ones. The conclusion is made that acetylcholinergic structures of the caudate nucleus play an important role in the central inhibitory mechanisms responsible for the extinction of nonreinforced reactions.     

NMDA channels control meal size via central vagal afferent terminals

The N-methyl-D-aspartate (NMDA) ion channel blocker MK-801 administered systemically or as a nanoliter injection into the nucleus of the solitary tract (NTS), increases meal size. Furthermore, we have observed that ablation of the NTS abolishes increased meal size following systemic injection of dizocilpine (MK-801) and that MK-801-induced increases in intake are attenuated in rats pretreated with capsaicin to destroy small, unmyelinated, primary afferent neurons. These findings led us to hypothesize that NMDA receptors on central vagal afferent terminals or on higher-order NTS neurons innervated by these vagal afferents might mediate increased food intake. To evaluate this hypothesis, we examined 15% sucrose intake after 50-nl MK-801 injections ipsilateral or contralateral to unilateral nodose ganglion removal (ganglionectomy). On the side contralateral to ganglionectomy, vagal afferent terminals would be intact and functional, whereas ipsilateral to ganglionectomy vagal afferent terminals would be absent. Three additional control preparations also were included: 1) sham ganglionectomy and 2) subnodose vagotomy either contralateral or ipsilateral to NTS cannula placement. We found that rats with subnodose vagotomies increased their sucrose intake after injections of MK-801 compared with saline, regardless of whether injections were made contralateral (12.6 +/- 0.2 vs. 9.6 +/- 0.3 ml) or ipsilateral (14.2 +/- 0.6 vs. 9.7 +/- 0.4 ml) to vagotomy. Rats with NTS cannula placements contralateral to nodose ganglionectomy also increased their intake after MK-801 (12.2 +/- 0.9 and 9.2 +/- 1.1 ml for MK-801 and saline, respectively). However, rats with placements ipsilateral to ganglionectomy did not respond to MK-801 (8.0 +/- 0.5 ml) compared with saline (8.3 +/- 0.4 ml). We conclude that central vagal afferent terminals are necessary for increased food intake in response to NMDA ion channel blockade. The function of central vagal afferent processes or the activity of higher-order NTS neurons driven by vagal afferents may be modulated by NMDA receptors to control meal size.     

Alimentary conditioned reflexes in the dog after pharmacologic activation and blockade of dopaminergic structures of the caudate nucleus

Bilateral injections of 60 mcg of amphetamine and dopamine into the head of caudate nucleus produced in dogs a manifested impairment of parameters of Pavlovian alimentary conditioned reflexes but did not influence the conditioned differential inhibition. Injections of 10 mcg of haloperidol were ineffective. The most effective were the influences on the dorsal part of the caudate nucleus head.     

Local cerebral blood flow following the intrastriatal administration of vasoactive intestinal peptide or peptide histidine isoleucine in the rat

The effect of the intrastriatal microinjection of either vasoactive intestinal peptide (VIP) or a related peptide-peptide histidine isoleucine (PHI)-on local cerebral blood flow in the striatum was examined using iodo[14C]antipyrine quantitative autoradiography. In 37 rats, an injection needle was inserted into a chronically implanted guide cannula and 1 microliter of vehicle, VIP or PHI was injected into the striatum. Blood flow in sham controls was reduced by 15% in proximity to the injection site, when compared with blood flow in the contralateral uninjected control side (P less than 0.01). Similarly, following PHI administration (20 pmol), blood flow in the striatum was reduced by 14% when compared to that contralaterally (P less than 0.02). In contrast, following VIP administration (20 pmol), blood flow in proximity to the injection site was increased compared to flow in the contralateral striatum in 4/8 animals with the mean flow being elevated by 10% (n.s.) compared to blood flow contralaterally. VIP and PHI had similar effects on local cerebral glucose utilization in the caudate nucleus, their response being equivalent to that of sham animals. These experiments suggest that VIP and PHI have a differential influence on the microvasculature of the caudate nucleus, with VIP but not PHI mediating cerebrovascular dilation.     

Effect of destruction of the hippocampus and caudate nucleus on the development of epileptic activity during corazole kindling

Experiments were carried out on random-bred white rats (250-350 g). Kindling was induced by daily intraperitoneal corazol injections in subthreshold (subconvulsive) doses (30 mg/kg). It has been demonstrated that bilateral hippocampal destruction did not change the seizure threshold, while bilateral caudate nucleus destruction lowered it. Hippocampal destruction delayed corazol kindling development and also accelerated the lowering of seizure susceptibility after corazol injections were discontinued, as compared to control animals. Caudate nucleus destruction induced more marked seizure reactions in the first 14 days after corazol injections were started. There were no significant differences in seizure manifestation severity in kindled and control groups. These data point to an essential role of caudate nucleus as an element of antiepileptic system and support the concept that hippocampus plays a role of pathologic determinant which is associated with the formation of an epileptic system underlying corazol kindling.     

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.