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The metabolic rate and vulnerability of dopaminergic neurons, and adenosine dynamics in the cerebral cortex, nucleus accumbens, caudate nucleus, and putamen of the common marmoset.

The pathophysiology of the striatum and cerebral cortex were studied from the pharmacological aspect. Investigation of the dopamine content in the cerebral cortex revealed that the premotor and motor area showed the highest level (61+/-6.2 ng/g). Intravenous injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) at a dose of 10 mg/kg reduced the dopamine content in the caudate nucleus and putamen to 2-3% of the control level in common marmosets, while it fell to 60% in the nucleus accumbens. There was no alteration of the dopamine content in the cerebral cortex. Immunohistochemical staining for tyrosine hydroxylase in the midbrains of MPTP-treated marmosets showed almost complete disappearance of dopaminergic cells from the substantia nigra and good preservation of cells in the ventrotegmental area. Dopaminergic cells projecting to the caudate/putamen, nucleus accumbens, and cerebral cortex showed marked, moderate, and no vulnerability to MPTP, respectively. After systemic administration of MPTP, dopaminergic neurons projecting to the caudate nucleus and putamen were damaged equally. However, the compensatory increase of dopamine turnover was more prominent in the putamen than in the caudate nucleus. Thus, nigroputaminal dopaminergic neurons may have a higher level of activity than neurons in the caudate. The neural connections and functions of the caudate nucleus and putamen have already been differentiated anatomically or physiologically. This compensatory increase of the dopamine turnover rate is another aspect of functional differences between the caudate nucleus and putamen. Investigation of the dopamine content in the head, body, and tail of the caudate nucleus showed no differences in the concentration of dopamine. However, a study of the metabolic rate of dopamine using alpha-methyl-p-tyrosine, a tyrosine hydoxylase inhibitor, showed higher metabolism of dopamine in the head of the caudate nucleus in common marmosets. Thus, dopaminergic neurons projecting to the caudate nucleus may show topographical differences in their firing rates. A microdialysis study indicated an increase in the metabolism of adenosine in the striatum of MPTP-treated animals. Cholinergic neurons are interneurons and are one of the main sources of adenosine in the striatum. Dopaminergic input from the substantia nigra acting on cholinergic neurons was decreased following MPTP treatment. The increase of adenosine metabolism suggested that cholinergic neurons in the striatum receive inhibitory inputs from nigrostriatal dopaminergic neurons.

Adenosine↗

Increased dopamine release in vivo in nucleus accumbens and caudate nucleus of the rat during drinking: a microdialysis study.

Changes in dopamine release and metabolism during drinking in thirsty rats were studied using in vivo microdialysis. Animals were maintained on controlled water (1 h per day) and trained to lick for water in a behavioural box. Microdialysis probes were then inserted into the left nucleus accumbens and right caudate nucleus through previously implanted guide cannulae, and the following day animals were connected for dialysis perfusion, during which they were allowed 1 h free access to water. Dopamine, and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, increased in both nucleus accumbens and caudate nucleus in association with drinking, but the 5-hydroxytryptamine metabolite, 5-hydroxyindoleacetic acid, only increased in the caudate nucleus. There was a direct correlation between the maximum dopamine release in nucleus accumbens and the maximum licking rate per 10-min period, but the maximum increase in dopamine did not occur until after the period of maximum licking. Increases in 3,4-dihydroxyphenylacetic acid and homovanillic acid were further delayed (by 20 and 30 min, respectively). In the caudate, changes in 5-hydroxyindoleacetic acid showed a very similar time-course to those of 3,4-dihydroxyphenylacetic acid. These data show that dopamine systems in both nucleus accumbens and caudate nucleus are activated in relation to drinking in thirsty rats. In addition, they indicate that 5-hydroxytryptamine systems in the caudate nucleus, but not in nucleus accumbens, may also be involved. The support that the results provide for the hypothesized connection between reward and limbic dopamine is discussed.

3,4-Dihydroxyphenylacetic Acid↗

Effects of locus coeruleus lesions on the release of endogenous dopamine in the rat nucleus accumbens and caudate nucleus as determined by intracerebral microdialysis.

Bilateral 6-hydroxydopamine lesions of the rat locus coeruleus (a) depleted forebrain norepinephrine levels by 67%, (b) reduced the basal release of dopamine in the nucleus accumbens and caudate nucleus by 26% and 19%, respectively, and (c) reduced (+)-amphetamine-induced release in the nucleus accumbens and caudate nucleus. The locus coeruleus appears to exert a tonic excitatory influence on striatal and limbic dopamine release in vivo.

3,4-Dihydroxyphenylacetic Acid↗

Efferent connections of the striatopallidal and amygdaloid components of the substantia innominata in the cat: projections to the nucleus accumbens and caudate nucleus.

Enkephalin immunoreactivity is used to divide the feline substantia innominata into circumscript subregions, i.e. the "striatopallidal system" and the "extended amygdala". In addition, enkephalin immunoreactivity is used to subdivide the striatopallidal system into two distinct areas, i.e. the subcommissural part of the globus pallidus displaying high enkephalin immunoreactivity and the ventral pallidum displaying moderate enkephalin immunoreactivity. The anterograde axonal transport of Phaseolus vulgaris-leucoagglutinin is used to study the efferents of these areas innervating the caudate nucleus and the nucleus accumbens. It is found that the enkephalin-immunoreactive subcommissural part of the globus pallidus as well as the dorsal enkephalin-immunoreactive regions of the extended amygdala project topographically along a rostrocaudal and mediolateral dimension to the nucleus accumbens. The far rostral parts of the caudate nucleus are found to be innervated by the subcommissural part of the globus pallidus whereas the extended amygdala has no such connection. This pathway is also found to be topographically organized along a mediolateral dimension. The non-enkephalin-immunoreactive area ventral and lateral to the subcommissural part of the globus pallidus is found to have no projections to the nucleus accumbens and caudate nucleus. This region rather innervates the olfactory tubercle. In contrast to the striatopallidal system the sublenticular part of the extended amygdala preferentially projects to the adjoining part of the extended amygdala, i.e. the bed nucleus of the stria terminalis. However, the ventral regions preferentially innervate the medial division of the bed nucleus of the stria terminalis whereas the dorsal regions preferentially innervate the lateral division of the bed nucleus of the stria terminalis. These data indicate that the differential forebrain systems represented in the feline substantia innominata, i.e. the striatopallidal system and extended amygdala have differential output stations. The results are discussed in view of the role of the subcommissural part of the globus pallidus and the nucleus accumbens in orofacial dyskinesia and schizophrenia, respectively.

Amygdala↗

The effects of 6-hydroxydopamine lesions of the nucleus accumbens and caudate nucleus of rats on feeding in a novel environment.

Open field activity and feeding behavior were studied in separate groups of rats 1 or 6 weeks after infusions of the neurotoxin, 6-hydroxydopamine (6-OHDA) into the nucleus accumbens or caudate nucleus. These infusions resulted in a specific destruction of the catecholamine innervation of the injected area. When compared with rats which received infusions of vehicle alone, both lesions resulted in a relative reduction in locomotor activity 1 week, but not 6 weeks, after the operation. Both lesions also resulted in a more rapid onset of feeding from wire baskets containing familiar laboratory chow. Rats with lesions of the nucleus accumbens also fed for longer, consumed more food, and fed in longer bouts than did sham-lesioned animals, but rats with lesions of the caudate nucleus did not. These data show changes in feeding behaviour produced by 6-OHDA infusions into the dopamine terminal fields which were long lasting in comparison with the locomotor impairments, and did not arise as a result of locomotor impairment. The differences in feeding behaviour may result from more general changes in behaviour such as an impairment in the reactivity to novel environmental stimuli or switching between types of behaviour.

Animals↗

Effects of microiontophoretic application of cocaine, alone and with receptor antagonists, upon the neurons of the medial prefrontal cortex, nucleus accumbens and caudate nucleus of rats.

The spontaneous extracellular electrical activity of 102 neurons, within the caudate nucleus (CN), medial prefrontal cortex (MPC), nucleus accumbens (NAc) and a control site, the lateral thalamic nucleus (LT), was studied. Cocaine depressed spontaneous activity in the majority of the cells studied from all regions except the lateral thalamus. Desipramine, which has been used clinically for the treatment of withdrawal of cocaine, also depressed neuronal activity in the caudate nucleus. In addition, of the three receptor antagonists tested, sulpiride, methysergide and naloxone, only the dopamine antagonist (sulpiride) affected cocaine-induced neuronal responses. This study further emphasizes the emerging importance of midbrain dopaminergic systems in the pharmacological effects of this important drug of abuse.

Animals↗

Organization of thalamic projections in the nucleus accumbens and the caudate nucleus in cats and its relation with hippocampal and other subcortical afferents.

The organization of thalamic projections in the nucleus accumbens (NA) and the caudate nucleus of cats and its relation to other subcortical striatal afferents were studied with a retrograde tracing technique by use of lectin-conjugated horseradish peroxidase. The study showed that the paraventricular and medial parafascicular nuclei (PF) of the thalamus project to the medial NA and the parataenial and medial PF project to the lateral NA. The ventral tegmental area and substantia nigra pars dorsalis (SNpd) project to medial and lateral NA. The midline thalamic nuclei, rostral intralaminar nuclei, ventroanterior nucleus, medial and lateral PF, lateral posterior complex, and nucleus limitans project to medial caudate nucleus. The most medial substantia nigra pars compacta (SNpc) and rostral SNpd project to medial caudate nucleus. The center median, ventrolateral, and the central lateral nuclei of thalamus, SNpc, and SNpd project to lateral caudate nucleus. These results suggest that the thalamic and subcortical nuclei known to connect with the limbic and frontal cortices project to NA and medial caudate nucleus. Those thalamic nuclei connected with the motor system project to lateral caudate nucleus. The hippocampus projects selectively to medial NA. The amygdala, raphe, and other mesencephalic nuclei project only to NA and medial caudate nucleus. The organization of hippocampal, amygdala, and other subcortical afferents suggests that NA and caudate nucleus can be separated into medial "limbic" and lateral nonlimbic "sensory-motor" compartments. A brief review of the distribution pattern of some neurotransmitters, neuropeptides, and their receptors and behavior studies provides additional support to the concept that the striatum can be divided into several subcompartments.

Amygdala↗

Neurotensin-sensitive protein phosphorylation in the rodent caudate nucleus.

1. Caudate nucleus slices from rat brain were prepared and incubated with 5 microM neurotensin for 30 seconds and 5 minutes. Following homogenization of the caudate nucleus slices, proteins were phosphorylated in vitro in the presence of CaCl2 or cyclic AMP. Phosphorylated proteins were separated by electrophoresis, and phosphate incorporation into individual proteins quantitated by microdensitometry of the resultant autoradiographs. 2. Incubation of caudate nucleus slices with neurotensin altered the subsequent in vitro calcium-dependent phosphorylation of several specific protein substrates, but in contrast, incubation with neurotensin altered the subsequent cyclic AMP-dependent phosphorylation of only 1 minor phosphoprotein substrate. 3. These results are consistent with other evidence which implicates calcium as an important intracellular mediator of the neurotensin signal.

Animals↗

Dopamine receptor blockade in nucleus accumbens or caudate nucleus differentially affects feeding induced by 8-OH-DPAT injected into dorsal or median raphe.

The 5-hydroxytryptamine (5-HT)1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) elicits a variety of behaviours including feeding in rats. These effects are accompanied by a reduction in 5-HT neurotransmission resulting from activation of somatodendritic 5-HT receptors located in the midbrain raphe nuclei. Previous work showing that dopamine receptor antagonists attenuate 8-OH-DPAT-induced feeding indicates that a facilitation of dopamine activity, secondary to reduced 5-HT activity, is involved in the expression of this effect. Microinjection studies were conducted to explore further the nature of this 5-HT-dopamine interaction. Injection of 8-OH-DPAT (0.125-2 micrograms) into either dorsal or median raphe induced dose-dependent increases in 1 h food intake in non-deprived rats. Pretreatment with haloperidol (0.05 and 0.1 mg/kg s.c.) attenuated the effect induced by median raphe 8-OH-DPAT (0.5 microgram) complementing previous results with dorsal raphe 8-OH-DPAT. The feeding resulting from dorsal raphe (1 microgram) or median raphe (0.5 microgram) 8-OH-DPAT was attenuated by alpha-flupenthixol (1.25 and 2.5 micrograms) injected into the nucleus accumbens. alpha-Flupenthixol in either the dorsolateral or ventrolateral aspects of the caudate nucleus attenuated also the feeding response to dorsal raphe, but not median raphe, 8-OH-DPAT. However, alpha-flupenthixol in the dorsomedial caudate failed to alter feeding resulting from dorsal raphe 8-OH-DPAT.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Toluene and telencephalic dopamine: selective reduction of amine turnover in discrete DA nerve terminal systems of the anterior caudate nucleus by low concentrations of toluene.

The present study demonstrates reductions of dopamine (DA) turnover in various areas of the anterior nucleus caudate of rat by toluene at concentrations lower than the current OSHA threshold limit value (100 ppm). Thus, toluene at low concentrations may produce disturbances in dopaminergic mechanisms of the basal ganglia probably leading to functional changes in sensory-motor integration. The increases in DA turnover in the cholecystokinin (CCK)-DA terminals of the subcortical limbic system induced by high concentrations of toluene may be part of the neurochemical basis for its abuse as a euphoric agent in man.

Animals↗

[Effect of microinjection of GABA into the caudate nucleus on electrical discharges of nociceptive neurons in caudate nucleus of rat].

The characteristics of glass microelectrode recorded electrical activity of nociceptive neurons in the caudate nucleus elicited by microinjection of GABA and blockage by picrotoxin (PIC) were studied in 53 Wistar rats. The results showed that GABA (25, 50, 100 micrograms/2 microliters every 2 min) inhibited the activity of pain excitation neurons (PEN), as shown by decreased frequency and increased latency, but enhanced the activity of pian, inhibition neurons (PIN), as shown by shortened duration and increased discharge frequency. Both activities are highly dose-dependent and could be blocked by PIC (i.p. 250 micrograms, 1 ml/1 min).

Animals↗

Effect of cholecystokinin-octapeptide on dopamine release from slices of cat caudate nucleus.

The cat caudate nucleus has been reported to possess a rich and fairly even distribution of nerve endings, containing both dopamine- and cholecystokinin-like peptides. In this study, the effect of cholecystokinin-octapeptide (CCK-8) on basal and electrically evoked tritium outflow from slices of cat caudate nucleus previously labeled with [3H]dopamine was examined. Evoked tritium outflow from slices of cat caudate nucleus was Ca2+ dependent and abolished by tetrodotoxin, suggesting that it reflects action potential-induced [3H]dopamine release. In the presence of bovine serum albumin and bacitracin, the sulfated but not the unsulfated form of CCK-8 inhibited both basal and electrically evoked tritium outflow from slices of cat caudate nucleus at very low concentrations. CCK-8 sulfate was efficient in causing this effect in concentrations down to 10(-14) M, and the maximum effect was obtained with 10(-11) M. In contrast, without bovine serum albumin and bacitracin, no inhibitory effect of CCK-8 sulfate was seen, but instead, a marked enhancement of tritium outflow at 10(-7) M was observed. The findings suggest that CCK-8 sulfate in dopamine/CCK coexistence regions is involved in regulating dopamine release.

Animals↗

The amphetamine-like releasing effect of the alkaloid (-)cathinone on rat nucleus accumbens and rabbit caudate nucleus.

1. (-)Cathinone, a new alkaloid from khat leaves, has recently been reported to have amphetamine-like behavioral effects. In order to investigate the effects of this compound on the cellular level, slices of rat nucleus accumbens, prelabelled with 3H-dopamine, were superfused with solutions of (-)cathinone. 2. It was found that (-)cathinone, as (+)amphetamine, enhanced the release of radioactivity from rat nucleus accumbens tissue. 3. In similar experiments on rabbit caudate nucleus it was observed that the catecholamine reuptake inhibitors benztropine, nomifensine and mazindol were able to block the (-)cathinone-induced release, indicating that the alkaloid has to penetrate to intraneuronal sites in order to evoke release. 4. It is concluded that the pharmacological similarity between (-)cathinone and (+)amphetamine extends to the cellular level and that the behavioral effects of (-)cathinone are due to stimulation of release from central catecholamine storage sites.

Alkaloids↗