Contribution of Blockade of the Noradrenaline Carrier to the Increase of Extracellular Dopamine in the Rat Prefrontal Cortex by Amphetamine and Cocaine

This study was performed to investigate the relative role of noradrenaline (NA) and dopamine (DA) carrier blockade in the effects of psychostimulants on DA transmission in the rat prefrontal cortex (PFCX). To this end, changes of extracellular DA and NA in the PFCX and of extracellular DA in the nucleus accumbens (NAc) were measured following the administration of amphetamine and cocaine, which are known to bind to both DA and NA carriers, or GBR 12909, a selective DA carrier blocker. After non-intravenous injection, amphetamine (0.25 and 0.5 mg/kg, s.c.) and cocaine (5 and 10 mg/kg, i.p.) increased extracellular DA in the PFCX to a larger extent than in the NAc, while the reverse applied to GBR 12909 (2.5 and 5 mg/kg, i.p.). These differences were obtained in spite of the fact that the three drugs elicited at each dose level a similar peak increase of extracellular DA in the NAc. Amphetamine and cocaine also increased extracellular NA in the PFCX and this effect was quantitatively similar to that on extracellular DA in the same area. Intravenous doses of cocaine and GBR 12909, corresponding to those which maintain self-administration in the rat, while equieffective in raising extracellular DA in the NAG, had different effects on extracellular DA in the PFCX. In fact, in contrast to cocaine, GBR 12909 increased extracellular DA in the PFCX to a lesser extent than in the NAc or did not modify it at all. The peak increase of extracellular DA in the PFCX was highly correlated to that of NA in the same area but was poorly correlated to the increase of extracellular DA in the NAc. These results suggest that amphetamine and cocaine increase extracellular DA in the PFCX largely through the blockade of the NA carrier. Direct evidence for this hypothesis was provided by the observation that, when the NA carrier was blocked by reverse dialysis of the PFCX with desipramine (1 μM), cocaine and GBR 12909 lost their differences in the ability to increase extracellular DA in the PFCX.     

刺激视上核对大鼠痛阈及电针镇痛的影响

以钾离子透引起的大鼠甩尾反应为痛指标，观察了电和化学刺激视上核（ＳＯＮ）对大鼠痛阈（ＰＴ）和电针（ＥＡ）镇痛的影响。电刺激ＳＯＮ后，ＰＴ明显高于假刺激组（Ｐ＜０．０５～０．００１），电刺激ＳＯＮ后电针足三里，镇痛效应明显提高，并有明显的量效关系。电刺激ＳＯＮ的近旁部位（０．５—１ｍｍ）对ＰＴ及电针镇痛无明显影响。ＳＯＮ内注射Ｌ－谷氨酸（Ｌ－Ｇｌｕ）后痛阈和电针镇痛效应都明显对照组，也有明显的量效关     

下丘脑弓状核注射神经降压素的镇痛效应及机制探讨

采用微量注射法,对37只大鼠进行了实验观察.结果如下:①下丘脑弓状核(ARC)注射神经降压素(NT)可使甩尾反应潜伏期(TFL)或痛阈显著升高.对照组注射生理盐水,TFL无明显变化.②ARC先注射纳洛酮,再注射NT,TFL变化值与单纯注射NT组相比明显下降.③ARC注射β-内啡肽(β-End)抗血清,再注射NT,TFL显著下降.④ARC注射生理盐水不影响注射NT的镇痛效应.上述结果表明,大鼠ARC注射NT可产生明显的镇痛效应,该效应可被ARC预先注射纳洛酮或β-内啡肽抗血清翻转,提示NT在ARC的镇痛作用,部分是由β-End介导的.     

Ultrastructural alterations in caudate nucleus in aged cats

These studies provide information on the changes in the ultrastructure in the caudate nucleus of aged cats. The major findings was that there was a decrease in the density of synapses in caudate neuropil. This decrease occurred in animals after 3 years of age and remained relatively constant in older animals. In conjunction with this change a population of unusually long synapses also occurred. These larger synaptic appositions were associated with enlarged spine heads. The caudate also showed a number of qualitative ultrastructural alterations. Many neurons contained accumulations of lipofuscin or lipopigment granules in aged animals. These inclusions occurred in both soma and dendrites of neurons and all types of glial cells. A unique configuration of collapsed agranular cisterns also was observed in aged animals. The present results indicate that decreases in synaptic density may by one morphological event underlying functional alterations observed in caudate neurons in aged cats.     

Timecourse of development of the wallaby trigeminal pathway. I. Periphery to brainstem

The development of the vibrissae and their innervation and the maturation of the brainstem trigeminal sensory nuclei have been studied in the wallaby, Macropus eugenii, from birth to adulthood. At birth, developing vibrissal follicles consist of solid epidermal pegs surrounded by dermal condensations. The developing follicles and adjacent skin are innervated by trigeminal afferents. Ten days after birth the follicle contains a dermal papilla and the deep vibrissal nerve can be recognised. A hair cone is present at postnatal day (P) 30 and hairs are apparent on the skin surface by P35. By P63 the deep vibrissal nerve can be seen innervating Merkel cells in the outer root sheath; in addition, the first signs of the blood sinus can be recognised. Innervation of the inner conical body and lanceolate and lamellated receptors supplying the mesenchymal sheath and waist region are not seen until P119, when the follicle resembles that seen in the adult. At birth, central processes of the trigeminal ganglion cells have entered the trigeminal tract and extend from the rostral pons to the upper cervical cord. Labelling with a carbocyanine dye at P0 shows afferents extending medially from the tract into the trigeminal subnuclei at all levels. At this stage the trigeminal nuclei appear as areas of increased cell density in the lateral brainstem. By P30–40 the four subnuclei can be distinguished on the basis of shape, cytoarchitecture, and succinic dehydrogenase reactivity. Adult morphology is not fully established until P210. In mature animals, nucleus principalis contains closely packed, polymorphic cells, frequently aligned parallel to thick fibre bundles that traverse the nucleus obliquely. Subnuclei oralis and interpolaris contain sparsely distributed, medium to large cells, randomly oriented, as well as prominent rostrocaudally directed fibre bundles. Subnucleus caudalis consists of the marginal layer, substantia gelatinosa, and magnocellular layers as described in other species. Patches of increased succinic dehydrogenase or cytochrome oxidase reactivity, presumably corresponding to the vibrissae, are present in subnuclei principalis, interpolaris, and caudalis in developing and adult animals, although the pattern is less clear than in rats. The brainstem patches are first seen at P40, approximately 6 weeks before the corresponding vibrissal-related pattern develops in the cortex. This suggests that the onset of patch formation may be regulated independently at different levels of the pathway. © 1994 Wiley-Liss, Inc.     

The effects of long-term, low-dose diazepam treatment on the guinea pig righting reflex and medial vestibular nucleus neuronal activity

Guinea pigs received a 2 mg/kg IP injection of diazepam, or an equivalent volume of vehicle, daily for 28–60 days. To determine whether tolerance developed to the ataxic effects of diazepam on the righting reflex, daily righting reflex latency (RRL) measurements were made before and 20, 30, and 40 min following the diazepam or vehicle injection for 28 days. Analyses of the RRLs for individual animals indicated that a significant decrease in RRL over time (indicating tolerance) occurred in only one out of nine animals receiving diazepam and in none of the vehicle animals. Medial vestibular nucleus (MVN) neurons in brain stem slices from animals receiving chronic diazepam treatment had a significantly higher average firing rate than those from vehicle controls. These results suggest that: a) long-term treatment with single 2 mg/kg daily IP injections of diazepam does not result in tolerance to diazepam's ataxic effects on the righting reflex in the majority of animals; b) this form of diazepam treatment may, nonetheless, induce a hyperactivity of brain stem MVN neurons that may be consistent with the occurrence of a withdrawal syndrome.     

电刺激黑质对脑干伤害性单位放电的影响

本实验采用单细胞外记录神经元单位放电的方法，在Ｗｉｓｔａｒ大鼠上观察到网状巨细胞核。一区伤害性神经元５７个，其中伤害兴奋性神经元（ＮＥＮ）４２个，伤害抑制性神经元（ＮＩＮ）１５个。电刺激黑质对ＮＥＮ（２９）和ＮＩＮ（８的放电呈抑制作用，其反应百分率分别由刺激黑质第１分钟时的１．０±２．１％和－２０．４±６．２％，降到第５分钟时的－８３．６±１２．３％和－６５．４±１０．７％（Ｐ＜０．０１）。刺激黑质对少数ＮＥＮ（１３）和ＮＩＮ（７）的放电有兴奋作用，其值分别由第］分钟时的２０．５±７．３％和１．０±３．４％，升高到第５分钟时的７４．５±１０．７％和２１，５±８．６％（Ｐ＜０．０５）。氟哌啶醇注入ＰＡＧ腹外侧部可阻断刺激黑质的效应，这提示从黑质到网状巨细胞核α－区存在着一条痛调制通路，而且这种通路的递质是多巴胺能的。     

Chronic Administration of Glucocorticoids Directly Upregulates Prepro-Neuropeptide Y and Y1-Receptor mRNA Levels in the Arcuate Nucleus of the Rat

The complete sequence of the cDNA encoding the neuropeptide Y (NPY) Y₁-receptor has recently been deduced from a rat brain library, and the presence of messenger ribonucleic acid (mRNA) encoding Y₁-receptor protein has been demonstrated within the brain. Using quantitative in situ hybridization histochemistry, the content and distribution of Y₁receptor and preproNPY mRNAs have been investigated in the hypothalamic arcuate nucleus of adrenalectomized rats receiving glucocorticoid replacement therapy for 12 days by means of either high doses of dexamethasone in their drinking water or by subcutaneous corticosterone pellets. Basal metabolic parameters such as weight gain or loss, blood glucose and plasma insulin were monitored: Dexamethasone treatment induced weight loss and a state of hyperinsulinemia with normoglycemia, while corticosterone treated animals displayed metabolic parameters identical to sham ADX animals. Within the arcuate nucleus of glucocorticoid treated animals, levels of Y₁receptor and preproNPY mRNAs were increased. In contrast, adrenalectomy itself had no effect upon Y₁-receptor mRNA levels or preproNPY mRNA levels in the arcuate nucleus. These studies demonstrate that glucocorticoids exert a stimulatory action on levels of Y₁-receptor mRNA and preproNPY mRNA levels in the hypothalamic arcuate nucleus. This is the first evidence to suggest that the expression of a neuropeptide-receptor gene in the central nervous system may be directly sensitive to peripheral hormonal signals.     

Effect of Zonisamide (CI-912) on a Synaptic System Model

The effect of the experimental antiepileptic drug zonisamide (1,2-benzisoxazole-3-methanesulfonamide, ZNS) on the trigeminal complex of cats was compared with the effect of established antiepileptic drugs. Intravenous administration of 10-40 mg/kg ZNS significantly depresses descending excitatory mechanisms, as well as segmental and descending inhibitory mechanisms, but has only a minor effect on segmental excitatory mechanisms. This spectrum of activity is similar to that of valproate, and suggests that ZNS should also be a broad-spectrum antiepileptic drug. In agreement with our experimental observations, it has been found that ZNS is effective against complex partial, generalized tonic clonic, and myoclonic seizures. The antiepileptic profile of ZNS in conventional screening tests resembles that of carbamazepine (CBZ) and phenytoin. However, CBZ exacerbates rather than prevents myoclonic seizures. Our experimental model thus provides a more accurate prediction of ZNS's clinical spectrum of activity. The relationship of these findings to the mechanism of action of antiepileptic drugs is discussed.     

A role of insular cortex in cardiovascular function

We sought to determine whether the insular cortex contributes to the regulation of arterial blood pressure (AP). Responses to electrical and chemical stimulation of the cortex were studied in the anesthetized, paralyzed, and artificially ventilated Sprague-Dawley rat. The insular cortex was initially defined, anatomically, by the distributions of retrogradely labeled perikarya following injections of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) into the nucleus tractus solitarii (NTS). Injections of WGA-HRP into the insular cortex anterogradely labeled terminals in cardiopulmonary and other divisions of the NTS and confirmed projections revealed by retrograde tracing experiments. Electrical stimulation of the insular cortex elicited elevations of AP (less than or equal to 50 mm Hg) and cardioacceleration (less than or equal to 40 bpm). The locations of the most active pressor sites corresponded closely to the locations of retrogradely labeled cells in layer V of granular and posterior agranular areas of the insular cortex (areas 14 and 13) and the extreme capsule. Maximal pressor responses were obtained at a stimulus intensity of three to five times threshold current of 20-30 microA. Responses elicited mostly with higher-threshold currents were also mapped in areas 2a and 5lb and the claustrum and within the corpus callosum. Unilateral injections into the insular pressor area of the excitatory amino acid monosodium glutamate (L-Glu; 0.05 nmol to 10 nmol) or the rigid structural analogue of L-Glu, kainic acid (KA) (0.4 nmol) (which specifically excite perikarya), caused topographically specific elevations in AP and tachycardia. During the course of the anatomical transport studies, new findings were obtained on the organization and characteristics of the cortical innervation of the NTS and the nucleus reticularis parvocellularis. Topographic relationships between the cortex and the NTS were organized in a more complex manner than previously thought. Cells projecting to caudal cardiopulmonary segments of the NTS were fewer and generally located ventrally and caudally and in a more restricted area than cells projecting rostrally or to the parvicellular reticular formation. Anterograde transport data revealed new presumptive terminal fields in dorsolateral, ventral, periventricular, and commissural regions of the NTS, including an area overlapping the terminal field of the aortic baroreceptor nerve. We conclude that neurons within an area of the insular cortex projecting to multiple brainstem autonomic nuclei, including a region of the NTS innervated by baroreceptor afferents, increase arterial blood pressure and heart rate.(ABSTRACT TRUNCATED AT 400 WORDS)