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1.
Modulation of the hippocampal alpha-adrenoceptor population by lesion of the serotonergic raphe-hippocampal pathway in rats 总被引:1,自引:0,他引:1
Electrolytic lesion of the ascending serotonergic fibers in the median raphe nucleus or in both the median raphe nucleus and dorsal raphe nucleus caused after 18 days more than 80% depletion of serotonin in the hippocampus and frontal cortex, respectively, without affecting norepinephrine and acetylcholine contents. alpha 1-Adrenoceptor binding of (3H) WB-4104 was increased in the hippocampus but not in the frontal cortex. Scatchard analysis revealed that the increase in (3H) WB-4101 binding in the lesioned hippocampus was the result of an elevated density of alpha 1-adrenergic receptors of about 65%. This phenomenon began 8 days postlesion and persisted for at least 90 days postlesion. Similar qualitative and quantitative results were obtained following chemical lesion of the serotonergic cells of origin in the median raphe nucleus with 5,7-dihydroxytryptamine. Selectivity of the phenomenon was further demonstrated as or beta-adrenoceptor binding with (3H) dihydroalprenolol and cholinergic muscarinic receptor binding with (3H) dexetimide were not significantly affected in the hippocampus. By comparison, when norepinephrine in the hippocampus was depleted by more than 90% by bilateral lesion of the ascending noradrenergic fibers with 6-hydroxydopamine (18 days), the alpha 1-adrenoceptor number was significantly increased by only about 20% while the beta-adrenoceptor number was enhance by 40%. The area-selective increase in alpha 1-adrenoceptor number in the hippocampus in the presence of unchanged norepinephrine content and in the absence of serotonin probably signifies that serotonin actively participates in the modulation of the noradrenergic receptor population. 相似文献
2.
Abstract: 5-HT1A autoreceptor antagonists enhance the effects of antidepressants by preventing a negative feedback of serotonin (5-HT) at somatodendritic level. The maximal elevations of extracellular concentration of 5-HT (5-HText ) induced by the 5-HT uptake inhibitor paroxetine in forebrain were potentiated by the 5-HT1A antagonist WAY-100635 (1 mg/kg s.c.) in a regionally dependent manner (striatum > frontal cortex > dorsal hippocampus). Paroxetine (3 mg/kg s.c.) decreased forebrain 5-HText during local blockade of uptake. This reduction was greater in striatum and frontal cortex than in dorsal hippocampus and was counteracted by the local and systemic administration of WAY-100635. The perfusion of 50 µmol/L citalopram in the dorsal or median raphe nucleus reduced 5-HText in frontal cortex or dorsal hippocampus to 40 and 65% of baseline, respectively. The reduction of cortical 5-HText induced by perfusion of citalopram in midbrain raphe was fully reversed by WAY-100635 (1 mg/kg s.c.). Together, these data suggest that dorsal raphe neurons projecting to striatum and frontal cortex are more sensitive to self-inhibition mediated by 5-HT1A autoreceptors than median raphe neurons projecting to the hippocampus. Therefore, potentiation by 5-HT1A antagonists occurs preferentially in forebrain areas innervated by serotonergic neurons of the dorsal raphe nucleus. 相似文献
3.
Presynaptic Nicotinic Cholinergic Receptors Labeled by [3 H]Acetylcholine on Catecholamine and Serotonin Axons in Brain 总被引:5,自引:0,他引:5
Nicotinic cholinergic receptor binding sites labeled by [3H]acetylcholine were measured in the cerebral cortices, thalami, striata, and hypothalami of rats lesioned by intraventricular injection of either 6-hydroxydopamine or 5, 7-dihydroxytryptamine. In addition, [3H]acetylcholine binding sites were measured in the cerebral cortices of rats lesioned by injection of ibotenic acid into the nucleus basalis magnocellularis. [3H]Acetylcholine binding was significantly decreased in the striata and hypothalami of both 6-hydroxydopamine- and 5,7-dihydroxytryptamine-lesioned rats. There was no change in binding in the cortex or thalamus by either lesion. Ibotenic acid lesions of the nucleus basalis magnocellularis, which projects cholinergic axons to the cortex, did not alter [3H]acetylcholine binding. These results provide evidence for a presynaptic location of nicotinic cholinergic binding sites on catecholamine and serotonin axons in the striatum and hypothalamus. 相似文献
4.
S Consolo H Ladinsky A S Tirelli V Crunelli R Samanin S Garattini 《Life sciences》1979,25(23):1975-1981
The anorectic agent, d-fenfluramine, maximally increased the acetylcholine content in the striatum by 50% at doses of 5–10 mg/kg. The action of the drug was completely prevented by treatments designed to interfere with serotonergic transmission (e.g., combined electrolytic lesion of the nucleus raphe medianus and dorsalis; pretreatments with methergoline, parachlorophenylalanine or fluoxetine). By contrast, interference with dopaminergic transmission (e.g., lesion of the nigrostriatal dopaminergic tract with 6-OHDA; pre-treatment with penfluridol) did not impede the action of d-fenfluramine. The administration of d-fenfluramine to animals given a supramaximal dose of apomorphine, 1.5 mg/kg, produced a summated increase in striatal acetylcholine. The data are consistent with the hypothesis that there may exist in the striatum different populations of cholinergic interneurons regulated by serotonin and dopamine, respectively. 相似文献
5.
The response of the serotonergic system following injury to the basal forebrain cholinergic system was investigated in rats. The density of 5-hydroxytryptamine (serotonin) type 2 (S2) receptor sites in the frontal cortex and hippocampus was determined 1 week and 4 months after production of lesions by injections of ibotenic acid into the medial septum and nucleus basalis magnocellularis. One week later, the number of S2 receptor sites in the frontal neocortex, as defined by [3H]ketanserin binding, was unchanged. Four months later, the number of [3H]ketanserin binding sites (and Bmax) was increased and high-affinity [3H]serotonin uptake was decreased in the frontal neocortex, but not in the hippocampus, relative to unlesioned controls. Choline acetyltransferase (acetyl-CoA:choline O-acetyltransferase; EC 2.3.1.6) activity was decreased significantly in the frontal neocortex and hippocampus 1 week and 4 months after surgery. The change in frontal neocortical S2 receptor site density was inversely related to the level of choline acetyltransferase activity, was specific for cholinergic denervation associated with the cortex but not the hippocampus, and may represent a localized denervation supersensitivity due to degeneration of median raphe cortical afferents. 相似文献
6.
Neurotoxin-induced lesion of the serotonergic raphe-hippocampal pathway produced about a 50% increase in the density of a nM affinity alpha-adrenergic binding site for (3H)WB-4101 in rat hippocampus 18 days postlesion without altering the specific binding of (3H)5-HT to serotonergic receptors. The chronic i.c.v. infusion of serotonin by minipump started at the appropriate time averted or reverted the effect. The dynamics of noradrenergic neurotransmission in the hippocampus was not impaired by lesion of the median raphe nucleus as determined by the uptake and turnover of noradrenaline as well as its release - as reflected by the normetanephrine concentration. In addition, neurotoxin-induced lesion of the dorsal noradrenergic bundle failed to alter either the Bmax or the Kd of (3H)WB-4101 binding to the nM site. Kainic acid-induced destruction of perikarya depressed the nM (3H)WB-4101 binding sites by 60% and completely prevented the up regulation caused by lesion of the median raphe nucleus. Thus, the supersensitivity-like response of the adrenoceptors to the lack of serotonin appears to be localized on kainate-sensitive cells within the hippocampus. 相似文献
7.
Interaction of propranolol with central serotonergic neurons 总被引:1,自引:0,他引:1
Central monoaminergic mechanisms are believed to be involved in cardiovascular regulation. The present study was designed to evaluate the involvement of central serotonergic pathways in the antihypertensive action of propranolol in pentobarbital anesthetized mongrel dogs. Ventriculocisternal perfusion of propranolol (25 ug/kg/min for 30 min) decreased serotonin turnover as indicated by a significant decrease in cerebrospinal fluid levels of 5-hydroxyindoleacetic acid (5-HIAA). This effect was accompanied by a significant reduction in mean arterial pressure and heart rate. These results indicate that propranolol decreases central serotonergic activity and suggests a possible role for central serotonergic pathways in the antihypertensive action of propranolol. Several studies have indicated that central serotonergic pathways participate in the regulation of blood pressure. Brainstem regions including the nucleus tractus solitarius, the raphe nucleus and the anterior hypothalamic preoptic region are involved in cardiovascular control and contain a dense population of serotonergic neurons. A centrally-mediated hypotensive effect of propranolol has been demonstrated. Centrally administered propranolol increases cerebrospinal fluid (CSF) levels of norepinephrine and reduces blood pressure possibly due to decreased peripheral sympathetic nerve activity. Central serotonergic pathways may also be involved in the antihypertensive action of some beta-adrenoceptor antagonists. Destruction of central serotonergic neurons with 5,7-dihydroxytryptamine and desipramine abolished the antihypertensive effect of intracisternal propranolol in sinoaortic denervated dogs. Acute administrations of (-)-propranolol and (-)-pindolol decreased the synthesis rate of serotonin, while acute administration of salbutamol, a beta 2-adrenoceptor agonist, increased 5-HIAA levels in rat brain structures. The present study was designed to evaluate the involvement of central serotonergic pathways in the antihypertensive action of propranolol. 相似文献
8.
Effect of immobilization stress on serotonin content and turnover in regions of the rat brain. 总被引:3,自引:0,他引:3
Sprague-Dawley rats were stressed by immobilization from 30 to 300 minutes and the effects on serotonin (5-HT) and 5-hydroxy-indoleacetic acid (5-HIAA) content were determined in the cerebral cortex, diencephalon, striatum, hippocampus and the brain stem. In a subsequent study 5-HT turnover rate in these brain areas was estimated by measuring 5-HIAA accumulation 0, 30, 60 and 90 minutes after probenecid. The content of 5-HIAA and the turnover rate of 5-HT were significantly increased in the cerebral cortex shortly after the onset of immobilization. The content of 5-HIAA in the brainstem was increased by immobilization although 5-HT turnover rate was not increased. Short term increases in 5-HIAA content were observed in the striatum and hippocampus. However, no significant changes in 5-HT turnover rate were observed in either of these 2 brain areas. Immobilization did not affect 5-HIAA content or 5-HT turnover in the diencephalon. The sensitivity of the serotonergic system in the cerebral cortex to immobilization stress suggests that this brain region could be used in future studies of the interrelationships between stress and the brain serotonergic system. 相似文献
9.
If the rat conflict test were a valid animal model of anxiety neurosis, evidence which implicates serotonin systems in the anxiety-reducing actions of benzodiazepine tranquilizers could be summarized as follows: (1) The punishment-lessening effects of benzodiazepines in the conflict test are mimicked by serotonin antagonists (methysergide, cinanserin, bromolysergic acid), serotonin synthesis inhibition (PCPA), and serotonin nerve terminal damage (5,6-dihydroxytryptamine). (2) Punishment effects may be intensified by the serotonin precursor, 5-hydroxytryptophan (in combination with a monoamine oxidase inhibitor), serotonin agonists (alpha-methyltryptamine), or intraventricular injections of serotonin itself. Intraventricularly administered serotonin also antagonizes the punishment-lessening effects of benzodiazepines. (3) Stimulation of the serotonergic cell bodies in the dorsal raphe nucleus by local application of crystalline carbachol causes intense suppression of behavior. The suppressive effects of raphe stimulation are antagonized by systemic administration of benzodiazepines. (4) In biochemical experiments, the decrease in norepinephrine turnover induced by oxazepam rapidly undergoes tolerance, whereas the decrease induced in serotonin turnover is maintained over repeated doses. These results parallel findings in the conflict test which indicate that the depressant action of oxazepam rapidly undergoes tolerance, whereas the anxiety-reducing action is maintained over repeated doses. Although central serotonin neurons are thus implicated in the therapeutic actions of benzodiazepine tranquilizers, it is quite possible that the drugs actually act indirectly to reduce serotonin activity. The concept that benzodiazepines may exert a primary action on GABA-containing neurons, which in turn regulate serotonergic transmission, was supported by preliminary psychopharmacological evidence. The GABA-antagonist picrotoxin, at doses that do not disrupt unpunished behavior, fully antagonizes the punishment-lessening effects of benzodiazepines in the conflict test. 相似文献
10.
Mizuo Takashima Masatoshi Takita Asami Umino Toru Nishikawa Hiroshi Mitsushio Kiyohisa Takahashi 《Neurochemistry international》1992,20(4):583-589
We investigated the effects of interruption of the impulse flow in the habenulopeduncular pathways by local infusion of tetrodotoxin on the acetylcholine and choline content in selected dopamine rich regions in the forebrain and midbrain in rats. The tetrodotoxin infusion caused a marked increase in acetylcholine content in the medial frontal cortex, striatum and ventral tegmental area+interpeduncular nucleus, but not in the limbic area or the substantia nigra, whereas choline content was reduced only in both the striatum and ventral tegmental area+interpeduncular nucleus. There was an increase in 3,4-dihydroxyphenylacetic acid content in the striatum after the manipulation. These findings suggest that the dorsal diencephalic conduction system may be involved in the integration of the activity of cholinergic neurons in the forebrain and midbrain regions and striatal dopanine neurons may play a role in the modulation of cholinergic neurons. 相似文献
11.
Dietmar Schmitz Tengis Gloveli Ruth M. Empson Uwe Heinemann 《Molecular neurobiology》1998,17(1-3):59-72
Among the molecular, cellular, and systemic events that have been proposed to modulate the function of the hippocampus and
the entorhinal cortex (EC), one of the most frequently cited possibilities is the activation of the serotonergic system. Neurons
in the hippocampus and in the EC receive a strong serotonergic projection from the raphe nuclei and express serotonin (5-HT)
receptors at high density. Here we review the various effects of 5-HT on intrinsic and synaptic properties of neurons in the
hippocampus and the EC. Although similar membrane-potential changes following 5-HT application have been reported for neurons
of the entorhinal cortex and the hippocampus, the effects of serotonin on synaptic transmission are contrary in both areas.
Serotonin mainly depresses fast and slow inhibition of the principal output cells of the hippocampus, whereas it selectively
suppresses the excitation in the entorhinal cortex. On the basis of these data, we discuss the possible role of serotonin
under physiological and pathophysiological circumstances. 相似文献
12.
Rats received a unilateral lesion of the nucleus basalis magnocellularis (NBM) by infusion of ibotenic acid. In addition, the dorsal raphe nucleus was lesioned by infusion of 5,7-dihydroxytryptamine (5,7-DHT). The release of acetylcholine (ACh), choline, serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) was measured in the frontal neocortex by means of microdialysis. Lesions of the NBM, but not the raphe nucleus, reduced the release of ACh significantly (–47%). The release of 5-HT and 5-HIAA was reduced by raphe lesions (–44% and –79%), but not by NBM lesions. In no case did the combined lesion affect neurotransmitter release more than a single lesion. These results suggest that serotonergic projections from the dorsal raphe nucleus are not involved in tonic inhibition of ACh release in the neocortex. 相似文献
13.
Additive effects of apomorphine and clonidine on serotonin neurons in the dorsal raphe 总被引:1,自引:0,他引:1
E H Lee 《Life sciences》1987,40(7):635-642
Effects of apomorphine (APO) and clonidine (CLON) on the mesostriatal and mesolimbic serotonergic systems were examined in the present study. Both drugs selectively elevated serotonin (5-HT) concentrations in the dorsal raphe and the striatum without significantly altering 5-HT measures in the median raphe and the hippocampus. Apomorphine also increased tryptophan and 5-hydroxyindoleacetic acid (5-HIAA) levels in the dorsal raphe and 5-HIAA level in the striatum. Clonidine did not markedly alter tryptophan and 5-HIAA measures, while it decreased 5-HT turnover rate in both region, as indicated by the ratio of 5-HIAA/5-HT levels. Co-administration of APO and CLON, at doses of each drug exerted maximum effects on 5-HT alone, produced an additive effect on 5-HT in the dorsal raphe, while their effects on 5-HT and 5-HIAA in the striatum were counteracting each other. Effects of APO on 5-HT and 5-HIAA were attributed to the elevation of 5-HT precursor tryptophan, while effects of CLON on 5-HT and 5-HIAA were due to a decreased rate of 5-HT turnover. Therefore, the present results support the hypothesis that the additive effects of APO and CLON on dorsal raphe 5-HT are mediated through different receptors and neuropharmacological mechanisms. 相似文献
14.
Differential Effects of Ipsapirone on 5-Hydroxytryptamine Release in the Dorsal and Median Raphe Neuronal Pathways 总被引:1,自引:1,他引:0
Abstract: Serotonergic neurons of the dorsal and median raphe nuclei are morphologically dissimilar. Recent results challenge previous evidence indicating a greater inhibition of dorsal raphe neurons after 5-hydroxytryptamine1A (5-HT1A ) autoreceptor activation. As both nuclei innervate different forebrain territories, this issue is critical to understanding the changes in brain function induced by anxiolytic and antidepressant drugs. Using microdialysis, we examined the modifications of 5-HT release induced by the selective 5-HT1A agonist ipsapirone in both neuronal pathways. Maximal and minimal basal 5-HT values (in the presence of 1 µ M citalopram) were 45.0 ± 4.8 fmol/fraction in the median raphe nucleus and 8.4 ± 0.4 fmol/fraction in the dorsal hippocampus. Ipsapirone (0.3, 3, and 10 mg/kg s.c.) reduced dose-dependently 5-HT in the two raphe nuclei and four forebrain areas. Maximal reductions (to ∼25% of predrug values) were observed in cortex and striatum and in median raphe nucleus. The effects were more moderate in dorsal and ventral hippocampus (to 66 and 50% of baseline, respectively). These results are consistent with a higher sensitivity of dorsal raphe neurons to 5-HT1A autoreceptor activation. Yet the differential reduction of 5-HT release in the median raphe nucleus and hippocampus suggests the presence of complex mechanisms of control of 5-HT release in these neurons. 相似文献
15.
The neostriatum (dorsal striatum) is composed of the caudate and putamen. The ventral striatum is the ventral conjunction of the caudate and putamen that merges into and includes the nucleus accumbens and striatal portions of the olfactory tubercle. About 2% of the striatal neurons are cholinergic. Most cholinergic neurons in the central nervous system make diffuse projections that sparsely innervate relatively broad areas. In the striatum, however, the cholinergic neurons are interneurons that provide very dense local innervation. The cholinergic interneurons provide an ongoing acetylcholine (ACh) signal by firing action potentials tonically at about 5 Hz. A high concentration of acetylcholinesterase in the striatum rapidly terminates the ACh signal, and thereby minimizes desensitization of nicotinic acetylcholine receptors. Among the many muscarinic and nicotinic striatal mechanisms, the ongoing nicotinic activity potently enhances dopamine release. This process is among those in the striatum that link the two extensive and dense local arbors of the cholinergic interneurons and dopaminergic afferent fibers. During a conditioned motor task, cholinergic interneurons respond with a pause in their tonic firing. It is reasonable to hypothesize that this pause in the cholinergic activity alters action potential dependent dopamine release. The correlated response of these two broad and dense neurotransmitter systems helps to coordinate the output of the striatum, and is likely to be an important process in sensorimotor planning and learning. 相似文献
16.
Serotonin Inhibits Acetylcholine Release from Rat Striatum Slices: Evidence for a Presynaptic Receptor-Mediated Effect 总被引:4,自引:2,他引:2
Rat brain striatum slices were incubated with [3H]choline, perfused with a physiological buffer, and stimulated by perfusion with a K+-enriched buffer for 2 min. The tritium overflow evoked by K+ was decreased by 5-hydroxytryptamine (serotonin, 5-HT) (maximal inhibition 10(-6) M). This effect of 5-HT was mimicked by several agonists (5-methoxytryptamine, N,N-dimethyl-tryptamine, bufotenin) and blocked by serotonergic antagonists (methiothepin, methysergide, cinanserin) but not by haloperidol; methiothepin and methysergide alone slightly increased the K+-evoked overflow of tritium (3H). Inhibition of the tritium release by 5-HT was not suppressed in the presence of tetrodotoxin (TTX) (10(-6) M). These results suggest that 5-HT tonically inhibits acetylcholine (ACh) release from striatal cholinergic neurons by acting on a presynaptic receptor localized on cholinergic terminals. 相似文献
17.
The actions of antimuscarinic agents (benztropine, trihexyphenidyl, and scopolamine) on the dynamics of acetylcholine (ACh) in central cholinergic neurons were examined in various rat brain areas. It was found that the pattern of changes in ACh turnover (TRACh) elicited by these drugs exhibited marked regional variations. After administration of the anticholinergic drugs, the TRACh in hippocampus and thalamus was increased, in cortex it was decreased, and in striatum it was unchanged. ACh concentration in the cortex and striatum was decreased while in hippocampus and thalamus ACh levels were unaltered. Further analysis of the cholinergic septo-hippocampal pathway using lesions of the fimbria-fornix and local drug injections into the septum argue against an in vivo action of these drugs on presynaptic or cell body muscarinic autoreceptors. Moreover, the data suggest that muscarinic receptor blockers cause an increased TRACh only in those areas where a feedback loop is operative, possibly by inhibiting a neuronal feedback loop involving at least one noncholinergic interneuron. 相似文献
18.
Triple fluorescence labelling was employed to reveal the distribution of chemically identified neurons within the pontine laterodorsal tegmental nucleus and dorsal raphe nucleus which supply branching collateral input to the central nucleus of the amygdala and hypothalamic paraventricular nucleus. The chemical identity of neurons in the laterodorsal tegmental nucleus was revealed by immunocytochemical detection of choline-acetyltransferase or substance P; in the dorsal raphe nucleus, the chemical content of the neurons was revealed with antibody recognizing serotonin. The projections were defined by injections of two retrograde tracers, rhodamine-and fluorescein-labelled latex microspheres, in the central nucleus of the amygdala and paraventricular nucleus, respectively. Neurons projecting to both the central nucleus of the amygdala and the paraventricular nucleus were distributed primarily within the caudal extensions of the laterodorsal tegmental nucleus and dorsal raphe nucleus. Approximately 11% and 7% of the labelled cells in the laterodorsal tegmental nucleus and dorsal raphe nucleus projected via branching collaterals to the paraventricular nucleus and central nucleus of the amygdala. About half of these neurons in the laterodorsal tegmental nucleus were cholinergic, and one-third were substance-P-ergic; in the dorsal raphe nucleus, approximately half of the neurons containing both retrograde tracers were serotonergic. These results indicate that pontine neurons may simultaneously transmit signals to the central nucleus of the amygdala and paraventricular nucleus and that several different neuroactive substances are found in the neurons participating in these pathways. This coordinated signalling may lead to synchronized responses of the central nucleus of the amygdala and paraventricular nucleus for the maintenance of homeostasis. Interactions between different neuroactive substances at the target site may serve to modulate the responses of individual neurons. 相似文献
19.
Serotonin and γ-Aminobutyric Acid Turnover After Injection into the Median Raphe of Substance P and D-Ala-Met-Enkephalin Amide 总被引:3,自引:2,他引:1
The raphe nuclei [which contain serotonin (5-HT) cell bodies] are also known to contain axons that store substance P, met-enkephalin, and gamma-aminobutyric acid (GABA). We have previously shown that GABA has a tonic inhibitory action on 5-HT turnover. To examine other possible interactions of these neuronal systems, we assessed the effect on 5-HT turnover of injecting substance P and 2-D-ala-met-enkephalin into the median raphe nucleus, and the effects of substance P on GABA turnover. Serotonin turnover was increased by 30% in the hippocampus after the injection of substance P (4 micrograms) into the median raphe, indicating an excitatory effect of substance P on the raphe-hippocampal system. Local injection of the metabolically stable metenkephalin analog 2-D-ala-met-enkephalin amide (10 micrograms) increased the hippocampal steady state content of 5-hydroxyindoleacetic acid (5-HIAA) by 60%. The data suggest an excitatory effect of met-enkephalin within the raphe nucleus. We attempted to estimate GABA turnover from the rate of disappearance of GABA after inhibition of glutamic acid decarboxylase by isoniazid and by the rate of accumulation of GABA after inhibition of GABA transaminase by gabaculine. Isoniazid, which is a competitive inhibitor, had too short and incomplete an action to be of use when injected intranuclearly. Gabaculine, which is an irreversible inhibitor, induced a rapid-onset increase in GABA content. This accumulation was linear up to 90 min. The injection fo gabaculine (80 ng) into the raphe increased GABA content by five times the control values, but hippocampal 5-HT and 5-HIAA contents were not significantly changed. Substance P injection increased the GABA turnover by 30%. Gabaculine seems a promising tool for detecting changes in GABA turnover. 相似文献
20.
The contents of acetylcholine and choline were determined in rat cortex, striatum, and hippocampus following intraventricular injection of β-endorphin or D-Ala2-enkephalinamide, a synthetic enkephalin analog, in doses known to produce analgesia in experimental animals. These opiate polypeptides produced significant increases in acetylcholine levels in the hippocampus, a subcortical structure rich in cholinergic terminals. The acetylcholine content of the hippocampus (but not the cortex or striatum) was significantly elevated 15, 30, and 60 minutes after a single intraventricular injection of β-endorphin (10 μg/brain) or D-Ala2-enkephalinamide (10 μg/brain). Peak alterations in regional acetylcholine concentrations and in analgetic effectiveness both occurred 30 minutes after peptide administration. Choline concentrations were unchanged by any of the experimental treatments. Naloxone hydrochloride (1 mg/kg, subcutaneously) affected neither brain acetylcholine concentrations, nor the response latencies of rats placed on a hot-plate; it did, however, antagonize the changes in these parameters caused by β-endorphin or D-Ala2-enkephalinamide. These data suggest that endorphins may normally regulate the physiologic activity of some cholinergic neurons. 相似文献