Significant changes in neuropeptide concentrations in the brain of normotensive (WKY) and spontaneously hypertensive (SHR) rats following knee joint monoarthritis

Changes induced by chronic monoarthritis in the nervous system was studied by measuring concentrations of substance P (SP)-, neurokinin A (NKA)-, calcitonin gene-related peptide (CGRP)- and neuropeptide Y (NPY)-like immunoreactivities in the brain and in the knee joints of control and monoarthritic normotensive (WKY) and spontaneously hypertensive (SHR) rats on day 21 after the induction of monoarthritis. Knee joint monoarthritis was induced by intra-articular injection of Freund's adjuvant into the right knee joint. The severity of arthritis was examined by measuring knee volumes and scratching behaviour and by X-ray. The right knee of both WKY and SHR monoarthritic rats had an increased volume and osteoporosis. SHR rats had more severe arthritis and increased scratching behaviour compared to the WKY. Tachykinins were significantly decreased in the hypothalamus of arthritic rats. In the pituitary higher concentrations of tachykinins and CGRP were found in the arthritic and/or control SHR rats than in the WKY. In the occipital cortex, striatum and hippocampus NPY was increased in monoarthritic rats. No correlation was found between neuropeptide concentrations in the brain and knee joints. Decrease of tachykinins and increase of CGRP to different degree in the hypothalamus and/or pituitary of the arthritic WKY and SHR rats indicates that these changes were selectively associated with the basal level of sympathetic tone and possibly related to the greater severity seen in SHR rats. The increase of NPY in the brain, not influenced by sympathetic tone, may be part of a general defence reaction to inflammation.     

Neuropeptide Levels after Pentylenetetrazol Kindling in the Rat

Levels of several neuropeptides were measured in the frontal cortex, dorsal hippocampus, striatum, and amygdala/pyriform cortex in rats kindled for 5 weeks by daily injection of pentylenetetrazol (30 mg/kg, i.p.). Significantly increased concentrations (by 30 - 140%) were found in all examined brain areas for neuropeptide Y, somatostatin (except hippocampus) and neurokinin-like immunoreactivity 10 days after the last kindling session. Similar but less pronounced changes were also found 24 h after the last seizure. The increase in total neurokinin-like immunoreactivity was due to a marked increase in neurokinin B as revealed by HPLC analysis. Increases in peptide levels, however, were restricted to fully kindled animals. At the same time no changes in levels of substance P, vasoactive intestinal polypeptide and calcitonin gene-regulated peptide were observed. Cholecystokinin octapeptide was enhanced only in the hippocampus (by 46%). The increases in neuropeptide Y, somatostatin, and neurokinin-like immunoreactivity subsided after 3 months. A markedly decreased seizure threshold was observed 10 days and 2 months after the final kindling session. No nerve cell degeneration was observed in kindled rats 24 h or 10 days after the last pentylenetetrazol injection. Some animals (2 of 4), however, exhibited signs of blood - brain barrier damage when examined 24 h after the last kindling session which may reflect the preceding convulsions. No such changes were detected after 10 days. The increases in peptide levels may suggest increased activity of respective neurons which, at least to some degree, may be associated with gamma-aminobutyric acid. The changes in peptide levels may be more closely related to the kindling procedure itself than to the decreased seizure threshold of the animals.     

Differences in regional brain concentrations of neuropeptide Y in spontaneously hypertensive (SH) and Wistar-Kyoto (WKY) rats

Regional brain concentrations of neuropeptide Y immunoreactivity (NPY) were measured in age-matched Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rats using a sensitive and specific radioimmunoassay developed within our laboratory. In 5 of the 9 brain regions examined the SH rats had significantly lower NPY levels compared to the WKY strain. The largest differences occurred within the cortex (−43%), and cervical (−30%) and thoracic spinal cord (−30%), whilst smaller differences were observed in the midbrain (−11%) and medulla oblongata-pons (−18%). The concentration of NPY in the hypothalamus and hippocampus did not vary between the strains. The SH rats contained significantly greater (+18%) NPY levels in the striatum compared to the WKY rats.     

Similar effects of substance P on learning and memory function between hippocampus and striatal marginal division

Substance P is an endogenous neurokinin that is present in the central and peripheral nervous systems. The neuropeptide substance P and its high-affinity receptor neurokinin 1 receptor are known to play an important role in the central nervous system in inflammation, blood pressure, motor behavior and anxiety. The effects of substance P in the hippocampus and the marginal di- vision of the striatum on memory remain poorly understood. Compared with the hippocampus as a control, immunofluorescence showed high expression of the substance P receptor, neuro- kinin 1, in the marginal division of the striatum of normal rats. Unilateral or bilateral injection of an antisense oligonucleotide against neurokinin 1 receptor mRNA in the rat hippocampus or marginal division of the striatum effectively reduced neurokinin 1 receptor expression. Indepen- dent of injection site, rats that received this antisense oligonucleotide showed obviously increased footshock times in a Y-maze test. These results indicate that the marginal division of the striatum plays a similar function in learning and memory to the hippocampus, which is a valuable addi- tion to our mechanistic understanding of the learning and memory functions of the marginal division of the striatum.     

Brain corticotropin-releasing factor immunoreactivity and receptors in five inbred rat strains: relationship to forced swimming behaviour

In the present work we studied the relationship between behaviour in the forced swimming test (FST), a test that presumably measures depressive-like behaviour in rodents, and central corticotropin-releasing factor (CRF) concentration and binding in five strains of rats. The strains were: Brown-Norway (BN), Fisher (FIS) 344, Lewis (LEW), spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). The FST data corresponding to the pretest showed significant inter-strain differences in both struggling and immobility: BN and WKY rats displayed lower levels of struggling and longer periods of immobility, LEW and SHR rats showed intermediate levels, and FIS rats were the most active. The results of the pretest were roughly similar to those observed in the test, the activity of WKY being extremely low. The CRF binding revealed significant inter-strain differences in prefrontal cortex and hippocampus, but not in cerebellum, pons-medulla or hypothalamus: in the prefrontal cortex, BN and FIS rats showed greater CRF binding than LEW, SHR and WKY rats; in the hippocampus BN rats showed higher levels of CRF binding than the other strains. The study of CRF content in various brain areas revealed inter-strain differences in prefrontal cortex and pons-medulla, but not in parietal-temporal cortex or in hypothalamus (CRF concentrations in the hippocampus were not detectable): CRF content in the prefrontal cortex was higher in BN than in the other strains, although the differences with FIS were not statistically significant; in the pons-medulla, FIS and LEW showed significantly higher CRF content than the other strains. From the present results it appears that BN and WKY rats were more prone to adopt passive strategies in the FST, but they did not show higher brain CRF immunoreactivity or down-regulation of CRF receptors. Hence, although there were inter-strains differences in all variables studied, no evidence for a relationship between the FST behaviour and central CRF activity was found.     

自发性高血压大鼠脑底动脉神经肽Y能神经纤维的分布

应用免疫组织化学技术ＡＢＣ法,对１０只雄性自发性高血压大鼠脑底动脉神经肽Ｙ能神经纤维分布进行了观察。在自发性高血压大鼠脑底血管的大脑前动脉、大脑中动脉、大脑后动脉和基底动脉壁上均可见棕褐色的免疫反应阳性纤维,纤维较粗,曲线状,呈网状分布,密度较高。与正常血压大鼠同一部位脑底动脉血管壁上的阳性纤维密度相比明显增加。结果表明：高血压大鼠脑底动脉各主要分支较正常血压大鼠脑底动脉各主要分支有更高密度的神经     

Regulation of Neuropeptides in Adult Rat Forebrain by the Neurotrophins BDNF and NGF

The expression of neuropeptides and neurotrophic factors is altered in the hippocampus after seizure induction in rats. Because the increase in brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) mRNAs precede changes in neuropeptide expression after seizure, it is possible that BDNF and NGF mediate subsequent alterations in peptide expression. To test this hypothesis directly, BDNF or NGF was infused into the hippocampus and cortex of adult rats. To ascertain the regional specificity of any observed effects of neurotrophin administration on neuropeptide expression, infusions into the striatum were also studied. To control for specificity, vehicle was also infused into the same sites. Peptide and mRNA alterations were assessed by Northern analysis, immunohistochemistry and radioimmunoassay. BDNF produced elevations of peptide and mRNA for neuropeptide Y and cholecystokinin in hippocampus and cortex, and somatostatin in cortex. BDNF increased mRNAs for neuropeptide Y, cholecystokinin, substance P and dynorphin in striatum. In contrast, BDNF decreased dynorphin peptide and mRNA in hippocampus. NGF's effects were limited to small mRNA increases, without corresponding changes in peptide levels, for neuropeptide Y in hippocampus and striatum, substance P in cortex and cholecystokinin in striatum. The distinct and limited effects of NGF infusion on neuropeptide expression demonstrate that BDNF's effects are not non-specific results of protein infusion into the brain. These findings indicate that BDNF may play a regionally specific role in modulating neuropeptide expression in the normal brain as well as in various pathophysiological states.     

Changes in tracheo-bronchial sensory neuropeptide receptor gene expression pattern in rats with cisplatin-induced sensory neuropathy

An attenuated neurogenic broncho-constriction underpinned by a decrease in sensory neuropeptide release has been shown to be characteristic of cisplatin-induced neuropathy. The present work was to explore if beyond neuropeptide release, cisplatin at a treatment schedule attaining sensory neuropathy, produced changes in the expression of the receptors of sensory neuropeptides such as somatostatin, calcitonin gene-related peptide (CGRP) and substance P (SP) in bronchial tissue of the rat. Twenty-four Wistar rats were divided into three groups. The animals in the "Treatment groups 1 and 2" were given cisplatin (1.5mgkg(-1)) and mannitol (75mgkg(-1)) over 5 days. The rats in the "Control" group were given mannitol+isotonic saline. Four animals from each group were used to study the expression pattern of the neuropeptide receptors in bronchial tissue. The levels of somatostatin receptor 4 (SSTR 4), neurokinin 1 (NK1), neurokinin 2 (NK2) and CGRP receptor expression were examined by quantitative real time polymerase chain reaction (RT-PCR) method, 11 and 22 days after the last cisplatin/vehicle dose. The cisplatin treatment significantly increased plasma somatostatin immunoreactivity and the expression of SSTR4 receptor detected both on the 11th and 22nd post-treatment days with no change in either CGRP, NK1, and NK2 receptor gene expression or plasma CGRP and substance P levels. We conclude that cisplatin neuropathy is accompanied by an increase in plasma somatostatin immunoreactivity with an increase in SSTR4 expression in rats.     

Amino acid and neuropeptide neurotransmitters in Huntington''s disease cerebellum

Several neuropathologic studies have suggested that there may be pathologic involvement of the cerebellum in Huntington's disease (HD). To investigate this further, we measured concentrations of neurotransmitter amino acids and the neuropeptides, somatostatin, neuropeptide Y and substance P, in HD cerebellar cortex and dentate nucleus. Twenty-seven pathologically confirmed cases of HD were compared with 20 controls. There were no significant changes in concentrations were significantly increased by 21% in HD cerebellar cortex. In the dentate nucleus, there were small significant increases of neuropeptide Y-like immunoreactivity and substance P-like immunoreactivity. The meaning of the neurotransmitter changes found is unclear: however, the lack of change in GABA and glutamate concentrations argues against a substantial loss of intrinsic cerebellar neurons.     

C-FOS expression in the rat brain in response to substance P and neurokinin B

Substance P, the principal neurokinin peptide in the mammalian brain and the natural ligand for the NK(1) tachykinin receptor, plays an integrative role in the regulation of cardiovascular, neuroendocrine and behavioural responses to stress. In rats, stimulation of periventricular NK(1) receptors in the forebrain induces a distinct pattern of cardiovascular responses which is accompanied by intense grooming behaviour. Ligands for NK(3) receptors induce a different pattern of cardiovascular and behavioural responses which comprises an increased release of vasopressin from the posterior pituitary and wet-dog shakes behaviour. To define the brain areas in the rat which respond to stimulation of forebrain NK(1) and NK(3) receptors and participate in the generation of these responses, the induction of c-Fos immunoreactivity was examined in brains following intracerebroventricular injections of substance P and neurokinin B in conscious rats. Stimulation of central NK(1) receptors by substance P (25, 100 and 500 pmol) injected into the lateral ventricle elicited grooming behaviour (face washing and hind limb grooming) and resulted in a marked c-Fos expression in the paraventricular, dorsomedial and parabrachial nuclei and in the medial thalamus. At 25 pmol, substance P did not significantly increase c-Fos expression, at 100 pmol, maximal c-Fos activation was induced in all four brain regions which responded to the peptide. Intracerebroventricular pretreatment of rats with the selective and high-affinity, non-peptide NK(1) receptor antagonist, RP 67580 (500 pmol), but not with its inactive enantiomer, RP 68651, completely abolished the behavioural response to substance P and reduced the substance P-induced c-Fos expression in all brain areas to nearly control levels. Intracerebroventricular injection of the natural ligand for NK(3) receptors, neurokinin B (500 pmol), elicited wet-dog shakes behaviour and activated c-Fos expression in localized regions of the forebrain including the organum vasculosum laminae terminalis, subfornical organ, median preoptic nucleus, paraventricular, supraoptic and anterior hypothalamic nuclei, medial thalamus and in the ventral tegmental area. These results demonstrate that the neurokinins, substance P and neurokinin B, induce specific and different patterns of c-Fos expression in distinct regions of the rat brain. Brain areas which selectively responded to substance P have been traditionally linked to the central regulation of cardiovascular and neuroendocrine reactions to stress or involved in the processing of nociceptive responses. On the other side, brain areas activated by neurokinin B are known to be involved in the central regulation of blood pressure, water and salt homeostasis or control of behaviour.     

Huntington's disease: changes in tachykinin content in postmortem brains

Substance P, neurokinin A, neuropeptide K, and neurokinin B were measured in both control (neurologically normal) and Huntington's disease brains obtained post mortem. All four peptides were significantly reduced in the substantia nigra of Huntington's disease patients compared with the control group. No differences were observed in frontal or temporal cortex except that neuropeptide K was significantly reduced in the frontal cortex of Huntington's disease cases. Correlation of the cell loss observed in the striatum and the tachykinin depletions detected in the substantia nigra in the Huntington's disease brains showed that the degree of cell loss agreed well with the extent of tachykinin depletion. Results of double-staining immunocytochemistry were consistent with the coexistence of substance P and neurokinin A in the substantia nigra of control brains and showed a marked depletion of immunoreactivity to both in Huntington's disease brains.     

Trimethyltin intoxication induces marked changes in neuropeptide expression in the rat hippocampus

In situ hybridization and immunocytochemistry were applied to investigate changes in the expression of somatostatin, neuropeptide Y, neurokinin B, cholecystokinin, dynorphin, and Met-enkephalin in the rat hippocampus after administration of a single peroral dose of trimethyltin hydroxide (9 mg/kg). Two time intervals were investigated: 5 days after trimethyltin treatment, when CA3 damage becomes manifest and is associated with increased aggression, seizure susceptibility, and memory deficit, and 16 days after trimethyltin, when neuronal damage is almost maximal and seizure susceptibility is declining. Robust but transient increases of neuropeptide Y, neurokinin B, and Met-enkephalin mRNA levels were revealed in the granule cell layer of the dentate gyrus and increased neuropeptide Y and neurokinin B immunoreactivities were found in mossy fibers. In reverse, dynorphin mRNA and immunoreactivity were decreased transiently in the dentate gyrus and mossy fibers, respectively. Strong over-expression of NPY mRNA was also observed in hilar interneurons and in CA1 and CA3 pyramidal cells as well as in the cortex at 5 days postdosing. Cholecystokinin- or neurokinin B-containing basket cells were preserved, while somatostatin-bearing interneurons were damaged by trimethyltin exposure. These neurochemical changes induced by trimethyltin intoxication strikingly parallel to those observed in animal models of temporal lobe epilepsy and may reflect activation of endogenous protective mechanisms. It is also suggested that hilar interneurons respond differently to trimethyltin exposure, for which neuropeptides are valuable markers. Synapse 29:333–342, 1998. © 1998 Wiley-Liss, Inc.     

Developmental changes of neuropeptides and amino acids in baboon cortex

The pattern of developmental changes in concentrations of substance P, somatostatin and neuropeptide Y immunoreactivity and amino acids was studied in baboon cortex. Samples of occipital or frontal neocortex were obtained from preterm (100-105 days gestation), near-term (170-176 days gestation), and young adult animals. Substance P concentrations were low at preterm, highest at near-term, and then declined to adult levels. Neuropeptide Y and somatostatin immunoreactivity increased steadily across the three age groups. Concentrations of aspartate and gamma-aminobutyric acid (GABA) also increased progressively from preterm to adulthood, whereas glutamate concentrations showed small increases that were not statistically significant. Concentrations of taurine and alanine were highest preterm and declined progressively to adulthood. Levels of neuropeptides and amino acids show distinct patterns of change during development of neocortex in the baboon.     

Central pressor actions of neurokinin B: increases in neurokinin B contents in discrete nuclei in spontaneously hypertensive rats

The regional distributions of neurokinin B-like immunoreactivity and substance P-like immunoreactivity in the central nervous system in spontaneously hypertensive rats (SHRs) and normotensive Wistar Kyoto rats (WKYs) were examined. The distribution of neurokinin B-like immunoreactivity in WKYs was not exactly the same as that of substance P-like immunoreactivity. The neurokinin B-like immunoreactivity contents of the supraoptic nucleus of the hypothalamus and the caudal part of the nucleus tractus solitarii were higher in SHRs than in WKYs. Injections of selective neurokinin B receptor peptides, senktide (suc-[Asp⁶,Me-Phe⁸]-substance P_6–11) and [Pro⁷]-neurokonin B, into the lateral brain ventricle of the normotensive rats caused dose-dependent increases in the blood pressure, and blockade of peripheral vascular vasopressin receptors reduced these pressor responses, but did not affect the substance P-induced pressor response. These findings suggest that the novel tachykinin peptide, neurokinin B has an important role in central pressor action in rats.     

Peptide neurons in the canine small intestine

The distributions of peptide-containing nerve fibers and cell bodies in the canine small intestine were determined with antibodies raised against seven peptides: enkephalin, gastrin-releasing peptide (GRP), neuropeptide Y, neurotensin, somatostatin, substance P, and vasoactive intestinal peptide (VIP). Immunoreactive nerve cell bodies and fibers were found for each peptide except neurotensin. In the muscle layers there were numerous substance P, VIP, and enkephalin fibers, fewer neuropeptide Y fibers, and very few GRP or somatostatin fibers. The mucosa contained many VIP and substance P fibers, moderate numbers of neuropeptide Y, somatostatin, and GRP fibers and rare enkephalin fibers. Nerve cell bodies reactive for each of the six neural peptides were located in both the myenteric and submucous plexuses. The distributions of nerve cell bodies and processes in the canine small intestine show many similarities with other mammals, for example, in the distributions of VIP, substance P, neuropeptide Y, and somatostatin nerves. There are some major differences, such as the presence in dogs of numerous submucosal nerve cell bodies with enkephalinlike immunoreactivity and of GRP-like immunoreactivity in submucous nerve cell bodies and mucosal fibers.     

Differential regulation of hippocampal progenitor proliferation by opioid receptor antagonists in running and non-running spontaneously hypertensive rats

Voluntary running in mice and forced treadmill running in rats have been shown to increase the amount of proliferating cells in the hippocampus. Little is known as yet about the mechanisms involved in these processes. It is well known that the endogenous opioid system is affected during running and other forms of physical exercise. In this study, we evaluated the involvement of the endogenous opioids in the regulation of hippocampal proliferation in non-running and voluntary running rats. Nine days of wheel running was compared with non-running in spontaneously hypertensive rats (SHR), a rat strain known to run voluntarily. On the last 2 days of the experimental period all rats received two daily injections of the opioid receptor antagonists naltrexone or naltrindole together with injections of bromodeoxyuridine to label dividing cells. Brain sections from the running rats showed approximately a five-fold increase in newly generated cells in the hippocampus, and this increase was partly reduced by naltrexone but not by naltrindole. By contrast, both naltrexone and naltrindole increased hippocampal proliferation in non-running rats. In non-running rats the administration of naltrexone decreased corticosterone levels and adrenal gland weights, whereas no significant effects on these parameters could be detected for naltrindole. However, adrenal gland weights were increased in naltrexone- but not in naltrindole-administered running rats. In addition, in voluntary running rats there was a three-fold increase in the hippocampal levels of Met-enkephalin-Arg-Phe compared with non-runners, indicating an increase in opioid activity in the hippocampus during running. These data suggest an involvement of endogenous opioids in the regulation of hippocampal proliferation in non-running rats, probably through hypothalamic-pituitary-adrenal axis modulation. During voluntary running in SHR naltrexone altered hippocampal proliferation via as yet unknown mechanisms.     

Myoelectric pattern and effects on small bowel transit induced by the tachykinins neurokinin A, neurokinin B, substance P and neuropeptide K in the rat

Effects of neurokinin A, neurokinin B, substance P and neuropeptide K on myoelectric activity in the small intestine were related to intestinal transit of a radioactive marker in fasted conscious rats. Myoelectric activity was recorded using bipolar electrodes implanted at 5, 20 and 35 cm distal to pylorus. Intravenous infusions of neurokinin A, neurokinin B and neuropeptide K at doses of 50–200 pmol kg^?1 min^?1 and substance P at doses of 100–300pmol kg^?1 min^?1, disrupted migrating myoelectric complexes and induced irregular spiking. These effects were not prevented by atropine, hexamethonium or mepyramine. However, the effect of neurokinin A was attenuated by spantide. The irregular spiking induced by the tachykinins was associated with increased transit of the marker in animals receiving neurokinin A and neurokinin B, but not substance P and neuropeptide K. We conclude that the tachykinins activate the smooth muscle layers of the small intestine in the rat by mechanisms involving neurokinin receptors, but not muscarinic, nicotinic or H₁-receptors. Our results suggest a role for tachykinins in regulation of motility by induction of irregular spiking, which may stimulate transit through the small intestine.     

Concentrations of putative neurovascular transmitters in major cerebral arteries and small pial vessels of various species

The levels of noradrenaline, neuropeptide Y, 5-hydroxytryptamine, and substance P were measured and compared between the large arteries of the circle of Willis and the small cerebral vessels of the pia mater in the rat, rabbit, cat, and monkey. In all species, noradrenaline and neuropeptide Y concentrations were greater in the larger arteries than in small pial vessels. Noradrenaline concentrations were dramatically reduced following cervical sympathectomy, with the extent of diminution differing greatly in the various species; the effects of cervical ganglionectomy on neuropeptide Y concentrations were less pronounced. 5-Hydroxytryptamine concentrations in rats, cats, and rabbits were significantly greater in the small pial vessels, although measurable concentrations existed in the circle of Willis. In cats and monkeys, substance P was found in major arteries, but was not detectable at the level of the small pial vessels. The differences in the regional distribution of the various neurotransmitter candidates in the cerebrovascular bed may reflect their physiological significance.     

Modulation of memory retention by neuropeptide K

Neuropeptide K (NPK) is one of the structures in β-preprotachykinin which also inclueds substance P. NPK, a 36 amino acid peptide, contains the sequence of neurokinin A as amino acids 27–36 of its C-terminus. Neurokinin A is also contained separately in the γ-preprotachykinin precursor. Both NPK (2.5–10 μg) and neurokinin A administered intracerebroventricularly after footshock avoidance training in the T-maze enhanced memory retention in CD-1 male mice. Local microinjections of NPK enhanced memory retention when injected into the rostral and caudal portions of the hippocampus (0.25 and 0.50 μg) and the amygdala (1.0 μg), but were without effect when injected into the septum and the caudate. The differential effects of NPK on memory retention across brains regions differed from those previously reported for substance P and neuropeptide Y. These studies suggest that NPK, acting through discrete anatomical areas, modulates memory processing. The functional significance of co-localization of neuropeptides with classical neurotransmitters and other transmitter peptides in the same neurons is not well understood, but recent studies have indicated that the neuropetides modulate the release of the primary transmitter. Since NPK occurs in the same precursor molecule as substance P, NPK may be co-released with the putative neurotransmitter substance P and act with it, in a synergistic manner, to enhance memory processing. These studies provide further evidence that the hippocampus is an anatomical structure involved in memory processing that occurs shortly after training.     

Neuropeptides and electroconvulsive treatment

Neuropeptides: corticotropin releasing factor (CRF), neuropeptide Y (NPY) and somatostatin (STS) have been associated with depression and anxiety, while neurotensin (NT), calcitonin gene-related peptide (CGRP) and tachykinins [neurokinin A (NKA) and substance P (SP)] are presumed to also play a role in the function of the dopaminergic system. Moreover, investigations in the past decade have shown that psychotomimetics and antipsychotic drugs as well as lithium affect brain synthesis, tissue concentrations, and release of some neuropeptides. In view of the above, experiments were carried out to explore whether changes in neuropeptides constitute one of the mechanisms of action of electroconvulsive treatment (ECT). Human cerebrospinal fluid (CSF) was studied before and after ECT, and brains from healthy and models of depression rats were investigated in electroconvulsive stimuli (ECS)-treated and sham-treated animals. The major findings were that a series of ECTs, in parallel to clinical recovery, increased CSF concentrations of NPY-like immunoreactivity (-LI), STS-LI, and CRF-LI, and in one study endothelin-LI. A series of ECS, but not a single treatment, reproducibly elevated concentrations of NPY-LI, NKA-LI, and STS-LI--but not NT-LI, SP-LI, galanin-LI, or CGRP-LI--in hippocampus, frontal cortex, and occipital cortex. No changes were measured in other regions, e.g., striatum. NPY and STS mRNAs were also increased indicating that ECS affects peptide synthesis. Generalized seizures induced by, e.g., kainic acid or pentylenetetrazole, had similar effects on neuropeptides. The changes persisted for at least 1 week after the last treatment. Pretreatment with compounds reducing seizures, such as benzodiazepines and MK-801; had no effect on magnitude of neuropeptide changes although the seizure duration was decreased by > 50%. On the basis of these findings, it is suggested that neuropeptides are involved in ECT's mechanisms of action. Since ECT is therapeutically efficient in both schizophrenia and depression and, taking into account that antipsychotic drugs and psychotomimetics as well as lithium selectively affect some neuropeptides, it is hypothesized that distinct combinations of neuropeptide and monoamine changes in selected neuronal populations constitute the underpinnings of ECT's effects on specific disease symptoms, conceivably independent of diagnosis.