Influences of cholecystokinin antiserum on the dopamine,norepinephrine and serotonin contents of different brain regions in rats

The effects of intraventricular administration of cholecystokinin antiserum on the dopamine (DA), norepinephrine (NE) and serotonin (5-HT) contents of the hypothalamus, mesencephalon, amygdala, septum, striatum and cerebral cortex were tested 24 hr following injection in rats.Cholecystokinin antiserum decreased the DA and NE contents of the hypothalamus, mesencephalon, amygdala and septum, while it increased the DA and decreased the NE content of the striatum. In the cerebral cortex the NE content was decreased. The 5-HT contents decreased in the mesencephalon, amygdala and septum, and increased in the striatum.     

Effects of 8-OHDPAT administration into the dorsal raphe nucleus and dorsal hippocampus on fear behavior and regional brain monoamines distribution in rats

The effects of R(+)-8-hydroxy-dipropylaminotetralin (8-OHDPAT) administration into the dorsal raphe nucleus (DRN) or bilaterally into the dorsal hippocampus (HIP) on fear behavior in a modified version of the light-dark transitions test and regional brain monoamines (NA, DA, 5-HT) and their metabolites (MHPG, DOPAC, 5-HIAA) in the hypothalamus, midbrain central gray matter, amygdala, hippocampus and pons were examined. The experiments were performed on 36 male, 3-month old Wistar rats. Administration of 8-OHDPAT (200 ng) into the DRN reduced time out from the illuminated part of the chamber and time of motionless behavior in the illuminated part, increased the number of returns from the dark to illuminated part and number of head dipping from the dark to illuminated part without effect on time of motionless behavior in the dark part and on time of locomotor activity in the illuminated as well as in dark part of the chamber. HPLC analysis showed reduction of 5-HT content in the midbrain and amygdala, reduction of 5-HIAA content in pons, increased 5-HIAA/5-HT ratio in the hippocampus and increased DOPAC/DA ratio in the hypothalamus, midbrain, hippocampus and pons without affecting the MHPG/NA ratio and NA content. The administration of 8-OHDPAT (100 ng per site) into the HIP reduced time out from the illuminated part of chamber, time of locomotor activity in the illuminated part and head dipping from the dark to illuminated part without effect on the number of returns from the dark to illuminated part, time of locomotor activity in the dark part and time of motionless in the illuminated as well as in the dark part of chamber. HPLC analysis showed reduction of NA content in the hypothalamus, amygdala and pons, increased the MHPG content in all the investigated structures, increased MHPG/NA ratio in all the investigated structures except the hypothalamus. Dopamine content decreased in the hypothalamus and amygdala, and DOPAC/DA ratio increased in the amygdala and hippocampus. Concentrations of 5-HT, 5-HIAA and 5-HIAA/5-HT ratio were unchanged. The results obtained indicate that 8-OHDPAT acting on the pre-synaptic 5-HT1A receptors decreases fear behavior and acting on 5-HT1A post-synaptic receptors increases fear behavior in the light-dark transitions test. The neurochemical base of anxiolytic and anxiogenic effects evoked by 8-OHDPAT is being discussed.     

Effects of different opiates on hypothalamic monoamine turnover and on plasma LH levels in pro-oestrous rats

Opiate inhibition of luteinizing hormone (LH) appears to involve changes in hypothalamic monoaminergic activity. Agonists of mu-, kappa- and sigma-opioid receptors and an opiate antagonist were administered at the onset of the preovulatory LH surge and their effects on hypothalamic monoamine turnover, and on plasma LH levels, investigated. The opiate antagonist, naloxone, significantly increased both noradrenaline (NA) turnover and plasma LH levels. Morphine (mu-agonist), significantly decreased NA concentration and plasma LH levels, but significantly increased dopamine (DA) and serotonin (5-HT) activity. Levorphanol (another mu-agonist) significantly decreased both NA and 5-HT concentrations and had no effect on circulating LH. Cyclazocine, ketocyclazocine and tifluadom (kappa-agonists) increased NA turnover but only tifluadom increased 5-HT turnover, also reducing LH levels significantly. N-Allylnormetazocine (SKF 10,047; sigma-agonist) increased 5-HT activity but did not alter LH levels. This study has confirmed the existence of a heterogenous group of opioid receptors within the hypothalamus which modulate monoamine neurotransmitters controlling LH release.     

Variations in extracellular monoamines in the prefrontal cortex and medial hypothalamus after modafinil administration: a microdialysis study in rats.

The role of brain amines in mediating the effects of the wake-promoting agent modafinil, used in the treatment of sleepiness associated with narcolepsy is still uncertain. Therefore we studied the effects of modafinil on extracellular serotonin (5-HT), dopamine (DA) and noradrenaline (NA), in rat prefrontal cortex and in the medial hypothalamus area. Modafinil (128 mg/kg i.p.) significantly increased waking in the first 4 h of EEG sleep recording. This cortical and behavioral activation was associated with an initial increase in extracellular 5-HT, DA and NA during the first 60 min following modafinil administration. In the prefrontal cortex, 5-HT release remained high for 3 h after modafinil administration. In contrast, in the hypothalamus, only NA release was enhanced while DA and 5-HT levels remained low. In a first step, modafinil may generate waking partly via cortical monoamine release, particularly DA and 5-HT, and also hypothalamic NA. In a second step, maintenance of waking might depend on hypothalamic NA.     

Biogenic amine levels in the mid-term human fetus

Spectrophotofluorometric assays were used to measure concentrations of DA, NA, 5-HT and 5-HIAA present in extracts of brain tissue and CSF taken from midterm gestational fetuses of both sexes. The presence of biogenic amines was demonstrated in fetuses as early as 10.5 weeks gestation. In the hypothalamus, the concentrations (expressed in ng/100 mg tissue) ranged from 10.2 to 62.2 for NA, 11.6 to 258.8 for DA, 7.6 to 38.6 for 5-HT and 56.6 to 114.1 for 5-HIAA. Concentrations of DA and 5-HT were found to be significantly (P less than 0.05) higher in the hypothalamus than in the cortex, but those of NA and 5-HIAA were similar in both areas. No sex difference was observed. The concentrations of biogenic amines in the CSF (expressed in ng/ml) were 63.1-286.7 for NA, 43.2-108.1 for DA, 30.9-87.5 for 5-HT and 8.0-42.8 for 5-HIAA.     

Dynorphin A enhances mitogen-induced proliferative response and interleukin-2 production of rat splenocytes

It has been well known that immune function is modulated by endogenous opioid peptides: beta-endorphin and enkephalins. However, the effect of dynorphin A on the immune function has not been well documented. In this study, we investigated dynorphin A in the regulation of mitogen-induced proliferation and and interleukin-2 (IL-2) production of rat splenocytes. The results showed that dynorphin A 1-13 as well as dynorphin A 1-17 enhanced concanavalin A-stimulated [(3)H] thymidine uptake 46-112% and IL-2 production in a dose-dependent fashion. These effects were reversed by naloxone and norBNI, a selective kappa-receptor antagonist. Dynorphin A reduced cyclic AMP contents in spenocytes in naloxone and norBNI reversible fashion. The data suggest that dynorphin A enhanced mitogen-stumulated lymphocyte proliferation and IL-2 production via kappa-opioid receptor and cAMP pathway.     

Brain monoamines in cases with Down's syndrome with and without dementia

Summary Three cases of Down's syndrome, one of which had a clinical history of a presenile dementia during final years, were analyzed for the content of tyrosine (Tyr), dopamine (DA), noradrenaline (NA), tryptophan (Try), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) in the following regions: the caudate nucleus, the putamen, the thalamus, the mesencephalon, and the hippocampus. A rather generalized reduction of DA, NA, 5-HT, and 5-HIAA was noted in the demented DS case.     

Catecholamines and serotonin in the rat central nervous system after 6-OHDA, 5-7-DHT and p-CPA

Summary The norepinephrine (NE), epinephrine (EPI), dopamine (DA) and serotonin (5-HT) contents were measured radioenzymatically in seven anatomically defined regions (frontal cerebral cortex, hippocampus, hypothalamus, midbrain, pons-medulla oblongata, cerebellum and spinal cord) in adult normal animals, after treatment with the tryptophan hydroxylase inhibitor p-chlorophenylalanine (p-CPA), and after the intraventricular administration of either 6-hydroxydopamine (6-OHDA) or 5, 7-dihydroxytryptamine (5, 7-DHT). The effects of p-CPA seemed not restricted to 5-HT, since reductions in catecholamine (CA) content were detected in several regions. After 5, 7-DHT given under desimipramine (DMI) protection, comparable reductions in 5-HT levels were obtained but the changes in CA were less severe than after p-CPA. The neurotoxin 6-OHDA decreased the CA in all regions but also 5-HT content in hippocampus, hypothalamus and ponsmedulla. The significance and the interpretation of these changes are discussed in relation to the specificity of the drugs employed, together with an assessment of the local monoamine turnover and the possible functional effects of monoamine interactions in the CNS.Abreviations CA catecholamines - NE norepinephrine - EPI epinephrine - DA dopamine - 5-HT serotonin - p-CPA para-chlorophenylalanine - 6-OHDA 6-hydroxydopamine - 5, 7-DHT 5, 7-dihydroxytryptamine     

Differential time course of effects of κ-opioid agonist treatment on dynorphin a levels and κ-opioid receptor density

The effects of κ-opioid agonist treatment on κ-opioid receptor density and on dynorphin A levels in the rat brain were studied. Rats were treated with the selective κ-opioid agonist U-69593 or vehicle for 5 d. Dynorphin A levels and κ-opioid receptor binding were measured on day 8 (3 d after the last injection) or 22 (17 d after the last injection). On day 8, κ-opioid receptor density was increased in the hypothalamus of rats treated with U-69593; there were no changes in the frontal cortex or caudate putamen. In contrast, there was an increase in dynorphin A levels in the frontal cortex and no changes in hypothalamus and caudate putamen in response to U-69593. On day 22, B _max was decreased in frontal cortex and caudate putamen of U-69593-treated rats, whereas dynorphin A levels were increased in the caudate putamen and in the frontal cortex. These findings suggest that κ-opioid receptor agonist treatment has long-term, continually changing effects on the κ-opioid system.     

Effects of H-Phe-Ile-Tyr-His-Ser-Tyr-Lys-OH on the in vitro uptake and release of radiolabelled dopamine, noradrenaline and serotonin in rat brain hypothalamic slices

The effects of H-Phe-Ile-Tyr-His-Ser-Tyr-Lys-OH, a hypothalamic heptapeptide with weak CRF activity were investigated on the in vitro uptake and release of radiolabelled dopamine (DA), noradrenaline (NA) and serotonin (5-HT) in rat brain hypothalamic slices. In a doses of 5 X 10(-6) M and 10(-5) M the heptapeptide significantly increased the 5-HT uptake, whereas it had no effect on the DA and NA uptakes. The same doses (5 X 10(-6) M, 10(-5) M) significantly increased the DA release without affecting the NA and 5-HT release. These results suggest that H-Phe-Ile-Tyr-His-Ser-Tyr-Lys-OH as a hypothalamic peptide is able to modulate selectively the activity of the serotonergic and dopaminergic transmission without influencing the noradrenergic system in the hypothalamus.     

Modulatory role for biogenic amines in the cerebral cortex. Microiontophoretic studies

In order to investigate the mode of action of biogenic amines in rat cerebral cortex, the unitary activity of spontaneously firing neurons and their excitatory response to acetylcholine (ACh) were examined using microiontophoretic administration of dopamine (DA), noradrenaline (NA) and serotonin (5-HT). The predominant effect of these biogenic amines on the spontaneous activity was a profound and prolonged inhibition of firing (2–4 min), which attained its maximum within 15–120 sec. This response was generally more abrupt in onset and of greater magnitude with NA and 5-HT than with DA. Most units inhibited by DA, NA and 5-HT also showed marked depression of their excitatory response to ACh when pretreated with these biogenic amines. With repetitive administration of ACh, it could be shown that the total duration of inhibition of ACh responses by DA and NA was not as prolonged as the inhibition of the spontaneous firing of the same cells. With 5-HT, the initial ACh responses of many neurons could be completely blocked, and this inhibitory effect lasted as long as the inhibition of spontaneous firing.In view of the anatomical data demonstrating a relative sparsity of monoamine nerve terminals in cerebral cortex, the strong inhibition induced by DA, NA or 5-HT may have reflected slow inactivation of the biogenic amines. However, it could also be indicative of underlying mechanisms of action dependent on metabolic changes. Indeed, the interaction between biogenic amines and ACh might imply a balance between the intracellular pools of cAMP and cGMP is directly or indirectly influenced by the biogenic amines and ACh, respectively. This hypothesis would not exclude other modes of local interaction between DA, NA, 5-HT and ACh, and appears compatible with the modulatory role of biogenic amines in cerebral cortex.     

Effect of morphine on dynorphin B and GABA release in the basal ganglia of rats

In vivo microdialysis was used to study the effects of systemic, as well as intracerebral administration of morphine and naloxone on dynorphin B release in neostriatum and substantia nigra of rats. The release of dopamine (DA), γ-aminobutyric acid (GABA), glutamate (Glu) and aspartate (Asp) was also investigated. Systemic injection of morphine (1 mg/kg s.c.) induced long-lasting increases in extracellular dynorphin B and GABA levels in the substantia nigra, whereas DA, Glu and Asp levels, measured in the same region, were not significantly affected. No effect on striatal neurotransmitter levels was observed following systemic morphine administration. Local perfusion of the substantia nigra with morphine (100 μM) through the microdialysis probe also increased nigral dynorphin B and GABA levels. Perfusion of the neostriatum with morphine (100 μM) significantly increased GABA and dynorphin B levels in the ipsilateral substantia nigra, but no effect was observed locally. Naloxone blocked the effect of systemic morphine administration on nigral dynorphin B and GABA release, already at a dose of 0.2 mg/kg s.c. Naloxone alone, given either systemically (0.2–4 mg/kg s.c.) or intracerebrally (1–100 μM), did not affect dynorphin B or amino acid levels, either in neostriatum or in substantia nigra. However, naloxone produced a concentration-dependent increase in DA levels. The present results indicate that systemic morphine administration stimulates the release of dynorphin B in the substantia nigra, probably by activating the μ-subtype of opioid receptor, since the effect of morphine on nigral dynorphin B and GABA was antagonized by a low dose of naloxone. The increase in extracellular DA levels produced by high concentrations of naloxone, both in neostriatum and substantia nigra, indicates a disinhibitory effect of this drug on DA release, probably via a non-μ subtype of opioid receptors located on nigro-striatal DA neurones.     

D-fenfluramine effects on hypothalamic monoamine activities and their hormonal correlates.

In order to test the hypothesis that the anorectic effects of D-fenfluramine involve mediation by increased serotonin (5-HT) activity we examined the effects of acute and chronic D-fenfluramine on the hypothalamic activities of 5-HT as well as the other major monoamine neurotransmitters noradrenaline (NA) and dopamine (DA). Precise and specific gas chromatograph/mass spectrometer analyses of NA, 5-HT and DA and their primary metabolites dihydroxphenylethyleneglycol (DHPG), 5-hydroxyindolacetic acid (5-HIAA) and dihydroxyphenylacetic acid (DOPAC), respectively, were made in combination with analysis of the hormonal correlates of the monoamines, glucose and adrenocorticotropin for NA, thyroid-stimulating hormone for 5-HT and prolactin for DA. Acute D-fenfluramine increased NA, while reducing 5-HT, functional activity. Chronic and acute after chronic, D-fenfluramine decreased both NA and 5-HT functional activity. The effect of acute D-fenfluramine on the DA system is consistent with a post-synaptic blockade which is compensated for by chronic treatment. Since chronic D-fenfluramine acted to depress noradrenergic tone, a further study was undertaken which showed that chronic D-fenfluramine does not impair the ability noradrenergic/sympathetic system to respond to stress. The results indicate that D-fenfluramine may not exert its anorectic and weight loss effects via serotonergic agonism and involvement of the NA and/or DA systems is likely.     

Involvement of noradrenergic and 5-hydroxytryptaminergic systems in allylnitrile-induced head twitching

Allylnitrile induces in rats persistent behavioral abnormalities, including head twitching, following a single administration. We studied the role of 5-hydroxytryptamine (5-HT) and noradrenaline (NA) systems in the brain of rats in inducing and maintaining the head twitching. Allynitrile (1.49 mmol/kg) induced 5-HT system activation in all areas of the brain studied 1–4 days after oral administration, and a reduction in the content of NA in the hippocampus, cortex and hypothalamus 1 day after dosing, in the hippocampus, cortex, hypothalamus and midbrain 2 days after dosing, and in the hypothalamus 4 days after dosing. Allylnitrile induced no change in the content of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA) or NA 7–28 days after dosing. Pretreatment with 5,7-dihydroxytryptamine (5,7-DHT) suppressed the allylnitrile-induced head twitching, and decreased the contents of 5-HT and 5-HIAA in almost all areas of the brain throughout the observation period, as well as the ratio of 5-HIAA/5-HT in the medulla oblongata plus pons from 1 to 30 days after dosing with allylnitrile. No change in NA was observed in any areas of the brain. Pretreatment withN-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) increased the head twitching induced by allylnitrile, and decreased the content of NA in all areas of the brain throughout the observation period, without any change in the contents of 5-HT or 5-HIAA or in the ratio of 5-HIAA/5-HT. The present results suggest the involvement of 5-HT and NA systems in allylnitrile-induced head twitching.     

Specificity and efficacy of noradrenaline, serotonin depletion in discrete brain areas of Swiss mice by neurotoxins

The aim of this work is to define neurotoxins doses to have efficient and specific depletion of noradrenaline (NA), serotonin (5-HT) neurotransmission in cortex, striatum, hippocampus and hypothalamus of Swiss mice after intraperitoneal administration of, respectively, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4) and para-chlorophenylalanine methyl ester hydrochloride (PCPA). The neurotransmitters concentrations were determined by high performance liquid chromatography with amperometric detection. The minimal single dose necessary to produce a highly significant decrease of NA levels (p<0.01 in comparison with control group) in hypothalamus (-44%), hippocampus (-91%), striatum (-40%) and cortex (-68%) was 50mg/kg but DA and 5-HT levels were modified, respectively, in hypothalamus and striatum. Three doses of PCPA 300 mg/kg over 3 consecutive days involve a profound depletion of 5-HT transmission in all discrete brain areas but NA and DA levels were also significantly reduced. In conclusion, DSP-4 has a different efficacy in discrete brain areas with a noradrenergic specificity which is not absolute, PCPA has a similar efficacy in all brain areas but is unspecific of 5-HT transmission.     

The effects of himantane and cycloprolylglycine on the enzymatic linkage of monoamine synthesis in the rat brain

Using HPLC we studied the effects of new substances with antiparkinsonian activities, viz., himantane and cycloprolylglycine (CPG), on the contents of monoamines and their metabolites in the brain structures of Wistar rats under conditions of the inhibition of tyrosine and tryptophan hydroxylases. It was shown that 70 min after administration himantane induces a significant decrease in the level of noradrenaline in the nucleus accumbens (NA) and striatum. At 70 min after administration of CPG, we observed an increase in the DOPAC/DA ratio in the NA and the level of 5-HIAA in the striatum. At 24 h after CPG administration, we observed an increase in the HVA content and HVA/DA ratio in the hypothalamus and striatum. We found a decrease in 5-HIAA in all brain structures we studied at 24 h after administration of CPG, which was absent at 70 min after injection of the substance; the magnitude of 5-HIAA/5-HT decreased in the hypothalamus, nucleus accumbens, and hippocampus. Our results suggest that both substances we studied influence serotonergic transmission by inhibition of the MAO B enzyme.     

Effects of capsaicin on central monoaminergic mechanisms in the rat

Summary The acute and chronic effects of capsaicin (s.c.) on the monoamines in the preoptic region + hypothalamus (RPO-H), spinal cord, substantia nigra and striatum were studied. Levels of DOPA, DA, DOPAC, HVA, 3-MT, NA, Trp, 5-HTP, 5-HT and 5-HIAA were determined by means of liquid chromatography (HPLC-EC). In response to acute capsaicin treatment, the levels of DA, DOPAC and DA synthesis rate (DOPA formation) were increased in a dose-dependent manner in the RPO-H and spinal cord. The disappearance rate of NA was accelerated in both regions. In substantia nigra, increased DOPAC levels were found whereas the levels of 3-MT were decreased in striatum after acute capsaicin treatment. Only minor changes on the levels of 5-HT and 5-HIAA in the regions studied were noted. Neonatal or adult capsaicin treatment failed to affect the levels of NA, DA and 5-HT (measured two months or five weeks after injection, respectively) in the regions studied. A capsaicin injection to rats pretreated with the drug as adults did not affect either the monoamines in the RPO-H and spinal cord or the body temperature. In contrast, in rats pretreated with capsaicin as neonates, a second injection of the drug to adult animals elicited hypothermia and changes in monoamines similar to those observed in naive animals.     

Effects of nitric oxide synthesis inhibition on methamphetamine-induced dopaminergic and serotonergic neurotoxicity in the rat brain

Summary We examined effects of nitric oxide (NO·) synthesis inhibition on methamphetamine (MA)-induced dopaminergic and serotonergic neurotoxicity. The toxic dose of MA (5 mg/kg, sc, X4) significantly decreased contents of dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum (ST), and significantly decreased contents of serotonin (5-HT) in the ST, nucleus accumbens (NA) and medial frontal contex (MFC). Coadministration with a NO· synthase inhibitor, N-nitro-L-arginine methyl ester (LNAME) (30 mg/kg, ip, X2), reduced the MA-induced decreases in contents of DA, DOPAC and HVA in the ST, but not reduced the MA-induced decreases in contents of 5-HT in the ST, NA and MFC. These findings suggest that the MA-induced dopaminergic, but not serotonergic neurotoxicity, may be related to the neural process such as NO· formation caused by the activation of postsynaptic DA receptor.     

Treatment of stroke with opiate antagonists — Effects of exogenous antagonists and dynorphin 1–13

We studied the effects of acute and long-term, continuous administration of six opioid compounds--naloxone, naltrexone, diprenorphine, leucine enkephalin, dynorphin 1-13, and dynorphin 3-13--on neurologic function, survival, and infarct size in a feline model of acute focal cerebral ischemia. Acutely, naloxone, naltrexone, and diprenorphine significantly improved motor function over baseline scores; the other drugs and saline (control) had no effect. In the long-term condition, no substance administered significantly affected level of consciousness, sensory function, or pupillary reactions. Naloxone, naltrexone, and dynorphin 1-13 significantly prolonged survival (p less than 0.1); the other substances had no effect. Evaluations of cat brains postmortem showed that the infarcts involved the sensory and motor cortex, internal capsule, and caudate nucleus. Infarct size was unaltered by any treatment administered; results among groups were remarkably similar. In evaluations of opiate receptor binding characteristics, high-affinity binding of ekylketocyclozocine was significantly reduced in the right (occluded) side of the cortex. Dynorphin 1-13 given 8 h postocclusion but before sacrifice increased this binding affinity to the previous level in non-occluded cortex. The observed protective effect of dynorphin 1-13 warrants further investigation. Our results support the involvement of endogenous opioid peptides in the pathophysiology of cerebral ischemia and suggest that, administered appropriately, opiate antagonists may be useful in the treatment of focal ischemic neurologic deficits.     

Effects of centrally administered neuropeptide Y (NPY) and NPY13–36 on the brain monoaminergic systems of the rat

Summary The effects of centrally administered NPY on the brain monoamine systems were investigated in the rat. Neuropeptide Y (0.2–5.0 nmol), its C-terminal 13–36 amino acid (a.a.) fragment, NPY_13–36 (0.4–10.0 nmol), or saline were injected into the right lateral cerebral ventricle of unrestrained rats. After l h the animals were decapitated, and the brains were taken out. Two cortical regions (frontal and parietal), the striatum, the hypothalamus, and the brain stem were dissected out. The tissue contents of noradrenaline (NA), dopamine (DA) and serotonin (5-HT), as well as of their major metabolites, 3-methoxy-4-hydroxy-phenylethylené glycol (MHPG), 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxy-indole acetic acid (5-HIAA) were measured. The most consistent finding was a dose-related increase of both DA and DOPAC levels after treatment with NPY. This effect was reproduced by NPY_13–36 in cortical tissue, whereas, in the sub-cortical regions, NPY_13–36 only reproduced the effects of NPY on the DOPAC levels. Less consistent effects were found on the NA systems, in which NA levels showed a tendency to increase following low, and decrease after high doses of NPY. These effects were largely reproduced by NPY_13–36. In addition, NPY increased tissue levels of MHPG in frontal cortical tissue in a dose-related manner. The brain 5-HT systems were not affected.