Biomedical subjects

Zbigniew S Herman

Publications and source records attributed to Zbigniew S Herman.

At least 19 recordsLinked to original sources

PubMed2006

Cytokines in schizophrenia and the effects of antipsychotic drugs.

Growing evidence suggests that the immune, endocrine, and nervous systems interact with each other through cytokines, hormones, and neurotransmitters. The activation of the cytokine systems may be involved in the neuropathological changes occurring in the central nervous system (CNS) of schizophrenic patients. Numerous studies report that treatment with antipsychotic drugs affects the cytokine network. Hence, it is plausible that the influence of antipsychotics on the cytokine systems may be responsible for their clinical efficacy in schizophrenia. This article reviews current data on the cytokine-modulating potential of antipsychotic drugs. First, basic information on the cytokine networks with special reference to their role in the CNS as well as an up-to-date knowledge of the cytokine alterations in schizophrenia is outlined. Second, the hitherto published studies on the influence of antipsychotics on the cytokine system are reviewed. Third, the possible mechanisms underlying antipsychotics' potential to influence the cytokine networks and the most relevant aspects of this activity are discussed. Finally, limitations of the presented studies and prospects of future research are delineated.

Antipsychotic Agents↗

PubMed2006

Effect of chronic treatment with perazine on lipopolysaccharide-induced interleukin-1 beta levels in the rat brain.

In the present study, we sought to determine whether chronic treatment with perazine alters lipopolysaccharide (LPS)-induced interleukin-1 beta (IL-1 beta) levels in the following rat brain regions: the hypothalamus, frontal cortex, striatum and hippocampus. Male Wistar rats were administered perazine dimaleate (15 or 30 mg/kg/day) in drinking water for 21 days. On day 22, LPS was injected i.p. (125 microg/kg) 2 h before decapitation. Concentrations of perazine and its metabolites in plasma and brain was assessed by HPLC. The levels of IL-1 beta were determined using ELISA. Treatment with perazine (30 mg/kg/day) reduced LPS-stimulated IL-1 beta levels in the hypothalamus, and a tendency to its decrease in the striatum and frontal cortex was observed. This in vivo study suggests for the first time that long-term oral administration of perazine modulates reactivity of cells producing IL-1 beta.

Animals↗

PubMed2006

Repeated treatment with antidepressants enhances dopamine D1 receptor gene expression in the rat brain.

Many pharmacological investigations have demonstrated that antidepressant agents profoundly affect serotonergic and noradrenergic neurotransmission. The molecular mechanisms by which these drugs exert their therapeutic action have not been clearly established. In our study, the possibility that antidepressant drug action is associated with dopamine neurotransmission was examined. To this end, the effect of 21-day treatment with 10 mg/kg of amitryptyline, mirtazapine and sertraline on the striatal and nucleus accumbens dopamine receptors was verified. The striatum and nucleus accumbens tissues were dissected 24 h after the last dose of the drug and total RNA was isolated. The expression of dopamine D1 to dopamine D5 receptors using reverse-transcriptase polymerase chain reaction (RT-PCR) procedure was compared to the glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) as constitutive gene activation internal control. Lab Works UV program has analyzed the mean optical density values of RT-PCR products. Statistical comparison of relative optical densities by a one-way analysis of variance (ANOVA) followed by Dunnett's test was performed. Despite their different pharmacological profiles, all three above-presented antidepressants significantly increased dopamine D(1) mRNA content. Our findings indicate that repeated antidepressant administration triggers induction of the brain dopaminergic receptors which is correlated with neuroadaptation of the brain dopaminergic pathway.

Amitriptyline↗

PubMed2006

Effects of short-term fenofibrate treatment on circulating markers of inflammation and hemostasis in patients with impaired glucose tolerance.

CONTEXT: Apart from lowering lipid levels, peroxisome proliferator-activated receptor (PPAR) alpha activators (fibrates) produce many other favorable effects that may contribute to their clinical effectiveness in dyslipidemic and diabetic patients. OBJECTIVE: The objective of this study was to compare the impact of a short-term treatment with fenofibrate and the American Heart Association (AHA) step 1 diet on systemic inflammation, hemostasis, and monocyte secretory function in relationship with their metabolic actions. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTIONS: This was a prospective, randomized, placebo-controlled trial involving the group of 91 ambulatory patients with impaired glucose tolerance (IGT) (diagnosed on the basis of the American Diabetes Association criteria), randomly divided into three groups, simultaneously treated for 30 d with the AHA step 1 diet (n = 30), micronized fenofibrate (267 mg/d, n = 31), or placebo (n = 30). The control group included 34 age-, sex-, and weight-matched subjects with normal glucose tolerance. Eighty-six (95%) patients and all control subjects completed the study. MAIN OUTCOME MEASURES: Plasma markers of inflammation and hemostasis and monocyte release of proinflammatory cytokines were measured. RESULTS: Compared with subjects with normal glucose tolerance, IGT patients exhibited higher plasma levels/activities of fibrinogen, factor VII, plasminogen activator inhibitor-1, high-sensitivity C-reactive protein, and oxidized low-density lipoproteins. Lipopolysaccharide-activated monocytes from IGT patients released significantly more TNF-alpha, IL-1beta, IL-6, and monocyte chemoattractant protein-1 in comparison with monocytes from control subjects. Thirty-day treatment with fenofibrate but not with the AHA step 1 diet: 1) improved lipid/lipoprotein profile and glucose metabolism, and 2) reversed or alleviated all the above-mentioned abnormalities. The favorable effects of fenofibrate on plasma high-sensitivity C-reactive protein and on monocyte release of TNF-alpha, IL-1beta, IL-6, and monocyte chemoattractant protein-1 did not correlate with its action on plasma lipids but was related to the improvement in insulin sensitivity and weakly to free fatty acid-lowering action. CONCLUSIONS: Our study is the first to show that relatively small disturbances in glucose metabolism are associated with marked and multidirectional abnormalities in plasma markers of inflammation and hemostasis and in monocyte secretory function. Moreover, fenofibrate may exhibit early pleiotropic effects in patients with IGT.

Adult↗

PubMed2005

Amitriptyline and nortriptyline inhibit interleukin-1 release by rat mixed glial and microglial cell cultures.

Pro-inflammatory cytokines, such as interleukin (IL)-1beta and tumour necrosis factor (TNF)-alpha have been suggested to be involved in the pathophysiology of depression and in the mechanism of action of antidepressant drugs. Until now the effect of antidepressants on cytokines has been examined only in plasma, blood mononuclear cells and spleen, which reflect the activity of peripheral cytokine network. The aim of this study was to evaluate the effect of amitriptyline and its metabolite nortriptyline on the release of IL-1beta and TNF-alpha by lipopolysaccharide (LPS)-activated rat mixed glial and microglial cell cultures. LPS stimulated the release of both cytokines. The exposure of mixed glial culture to amitriptyline and nortriptyline led to a decrease in both IL-1beta and TNF-alpha release. Moreover, amitriptyline reduced LPS-stimulated IL-1beta release by microglial cultures. Although amitriptyline reduced secretion of both cytokines, the drug did not affect IL-1beta and TNF-alpha mRNAs in mixed cell cultures. Our study has shown for the first time that amitriptyline and nortriptyline administered at concentrations which may be achieved in plasma and brain structures during treatment, inhibit the secretion of IL-1beta and TNF-alpha in rat mixed glial and microglial cell cultures. The obtained results support the previous observations that antidepressants are able to reduce peripheral release of pro-inflammatory cytokines and suggest that the cytokine network may be involved in the central mechanism of action of amitriptyline and nortriptyline.

Amitriptyline↗

PubMed2005

Chlorpromazine and loxapine reduce interleukin-1beta and interleukin-2 release by rat mixed glial and microglial cell cultures.

The cytokines IL-1beta and IL-2 are released from activated glial cells in the central nervous system and they are able to enhance catecholaminergic neurotransmission. There is no data concerning influence of antipsychotics on glial cell activity. Antipsychotics reaching the brain act not only on neurons but probably also on glial cells. The aim of this study was to evaluate the effect of chlorpromazine and loxapine on release of IL-1beta and IL-2 by mixed glial and microglial cell cultures. Chlorpromazine in concentrations 2 and 20 muM, and loxapine 0.2, 2 and 20 microM reduced IL-1beta secretion by LPS-activated mixed glia cultures after 1 and 3 days of exposure. Chlorpromazine in concentrations of 0.2, 2 and 20 microM reduced the IL-2 secretion in mixed glial cultures after 3 days of exposure. Loxapine in concentrations of 0.2, 2 and 20 microM reduced IL-2 secretion in mixed glia cultures after 1 and 3 days of exposure, and additionally loxapine decreased IL-1beta and IL-2 secretion in LPS-induced microglia cultures in concentrations of 2, 10 and 20 muM. Quinpirole-a D2 dopaminergic agonist increased LPS-induced IL-1beta and IL-2 secretion in mixed glia cultures only in the highest dose of 20 microM. These findings suggest the absence of functional dopamine receptors on cortical microglial cells. Mixed glia cultures deprived of microglia (by shaking and incubating with L-leucine methyl ester) did not release IL-1beta and IL-2. This observation suggests that microglia can be a source of assessed cytokines. Results of the present study support the view that antipsychotics act not only on neurons but also on glial cells. However, the clinical significance of these observations still remains unclear.

Analysis of Variance↗

PubMed2005

Effect of monthly atorvastatin and fenofibrate treatment on monocyte chemoattractant protein-1 release in patients with primary mixed dyslipidemia.

The aim of this study was to compare the effect of 30-day treatment with atorvastatin and fenofibrate on monocyte release and plasma levels of monocyte chemoattractant protein-1 (MCP-1). We studied 52 atherosclerotic patients with primary mixed dyslipidemia and 16 age-, sex-, and weight-matched control subjects with asymptomatic atherosclerosis. Dyslipidemic patients enrolled into the study were randomly divided into three groups, simultaneously treated with atorvastatin (20 mg/d, n = 18), fenofibrate (267 mg/d, n = 16), or placebo (n = 18). Plasma lipid-profile and content of MCP-1, and monocyte release of this chemokine were measured at baseline and after 30 days of therapy. Compared with the control subjects, dyslipidemic patients exhibited the increased plasma levels and monocyte MCP-1 release. Atorvastatin and fenofibrate not only improved lipid profile but also decreased monocyte secretion of this chemokine. Moreover, hypolipemic agents slightly reduced its plasma levels. MCP-1-lowering effect of atorvastatin and fenofibrate did not correlate with the lipid-lowering potential of these agents. Our results suggest that atorvastatin and fenofibrate produce their antiinflammatory effect partially via inhibiting monocyte release of MCP-1. The treatment-induced reduction in its secretion may contribute to the clinical effectiveness of statins and fibrates in the therapy for atherosclerosis and other chronic fibroproliferative diseases.

Adult↗

PubMed2005

Monocyte release of tumor necrosis factor-alpha and interleukin-1beta in primary type IIa and IIb dyslipidemic patients treated with statins or fibrates.

Both 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) as well as peroxisome proliferator-activated receptor (PPAR)alpha activators (fibrates) proved to be effective in the primary and secondary prevention of cardiovascular diseases. The benefits of hypolipemic therapy in cardiovascular diseases cannot be explained only by the lipid-lowering potential of these agents. The aim of this study was to clarify the effect of hypolipemic agents on proinflammatory cytokine release from human monocytes in relationship with their action on plasma levels of sensitive systemic marker of low-grade vascular inflammation. Plasma lipid and high-sensitivity C-reactive protein (hsCRP) levels, and the release of tumor necrosis factor-alpha (TNFalpha) and interleukin-1beta from monocytes were assessed at baseline and 30 and 90 days following randomization of IIa dyslipidemic patients into fluvastatin or simvastatin groups and randomization of type IIb dyslipidemic patients to the micronized form of either ciprofibrate or fenofibrate. Lipopolysaccharide-stimulated monocytes from dyslipidemic patients released significantly more TNFalpha (types IIa and IIb dyslipidemias) and interleukin-1beta (type IIa dyslipidemia) in comparison with monocytes in 59 age-, sex-, and weight-matched control subjects. Their baseline hsCRP levels were also higher. Both statins and fibrates reduced the release of TNFalpha and interleukin-1beta, and lowered plasma hsCRP levels. The effects of hypolipemic agents on cytokine release and plasma hsCRP were unrelated to their lipid-lowering action. Our results have demonstrated that type IIa and IIb dyslipidemic patients exhibit the abnormal pattern of TNFalpha and interleukin-1beta production by activated monocytes. Both HMG-CoA reductase inhibitors and PPARalpha activators normalize monocytic secretion of these cytokines, and this action may partially contribute to the systemic antiinflammatory effect of hypolipemic agents. The statin- and fibrate-induced suppression of proinflammatory cytokine release from monocytes seems to play a role in their beneficial effect on the incidence of cardiovascular events.

Adult↗

PubMed2004

The effect of statins and fibrates on interferon-gamma and interleukin-2 release in patients with primary type II dyslipidemia.

The aim of the study was to assess the effect of two major groups of hypolipemic drugs, HMG-CoA reductase inhibitors (statins) and PPARalpha activators (fibrates), on the secretory function of T-lymphocytes in patients with primary type II dyslipidemia. Sixty-three patients with type IIa dyslipidemia were randomized to fluvastatin (40 mg daily; n = 33) or simvastatin (20mg daily; n = 30), while 68 type IIb dyslipidemic patients were treated with micronized ciprofibrate (100mg daily; n = 34) or micronized fenofibrate (200mg daily; n = 34). Lipid profile and cytokine (interferon-gamma and interleukin-2) release by phytohemagglutinin-stimulated lymphocytes were determined at the beginning of the study and after 30 and 90 days of treatment. Compared to healthy subjects (n = 59), both type IIa and IIb dyslipidemic patients exhibited higher baseline release of interferon-gamma and interleukin-2. Fluvastatin, simvastatin and, to a less extent, ciprofibrate and fenofibrate inhibited the release of both cytokines, but this effect did not correlate with their lipid-lowering potential. Hypolipemic agents also slightly reduced plasma interleukin-2 levels. Our study suggests that the beneficial effect of hypolipemic drugs involves their inhibitory action on the secretory function of T-lymphocytes. This lipid-independent action is stronger for statins than for fibrates and probably results from their "class" effect. The treatment-induced reduction in the release of both cytokines may contribute to the clinical effectiveness of statins and fibrates in the therapy of atherosclerosis and in the management of organ transplant recipients.

Adult↗

PubMed2004

Does neuropeptide Y (NPY) mediate the effects of psychotropic drugs?

Although several studies have summarized the effects of neuropeptide Y (NPY) in the central nervous system, its role in psychopharmacotherapy has not been reviewed in detail. For the last few years, there has been an increase in the number of studies on the suggested role of NPY in the benefits of treatment for mental disorders. Our review focuses on the possible involvement of altered NPY system activity in the effects of antianxiety, antidepressant and antipsychotic therapies. Potential sites and receptors, which are implicated in mediating the NPY effects of psychotropic drugs, have been described. We discuss the significance of alterations in the brain NPY system for the development of new methods of treatment for mental disorders.

Anti-Anxiety Agents↗

PubMed2003

Flupentixol and trifluperidol reduce secretion of tumor necrosis factor-alpha and nitric oxide by rat microglial cells.

Tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO), both of which are produced by activated microglial cells, are involved in the neuropathogenesis of many diseases affecting the central nervous system (CNS). There is a need to develop drugs that inhibit neurotoxic processes in neurodegenerative diseases. The aim of this study was to evaluate the effect of two neuroleptics, flupentixol and trifluperidol, on the release of pro-apoptotic TNF-alpha and NO by LPS-activated rat microglial cells. Flupentixol and trifluperidol reduced the TNF-alpha and NO release by cultured microglia exposed to LPS for 6 and 24h. The results suggest that flupentixol and trifluperidol, which are well-known antipsychotic drugs, may be used in the treatment of CNS diseases associated with excessive TNF-alpha and NO release.

Animals↗

PubMed2002

Methionine-enkephalin and leucine-enkephalin increase interleukin-1 beta release in mixed glia cultures.

Interleukin-1 beta (IL-1 beta) is synthesized in the brain in response to LPS. Excessive IL-1 beta expression is observed in neurodegenerative diseases. The aim of this study was to evaluate the effects of methionine-enkephalin (ME) and leucine-enkephalin (LE) on the baseline and LPS-activated release of IL-1 beta in rat mixed glia cultures. ME and LE increased LPS-induced IL-1 beta release, which was not blocked by naloxone. Both ME and LE increased the baseline release of IL-1 beta, which was completely blocked by naloxone pretreatment. Mixed glia cultures deprived of microglia (by shaking and incubating with L-leucine methyl ester) did not release IL-1 beta, which indicates microglia as a source of the changes in IL-1 beta release. The results of the study suggest that neurons may regulate glial activity through releasing enkephalins.

Animals↗

PubMed2002

[Pleiotropic effects of micronized fenofibrate in patients with combined hyperlipidemia].

More and more recent studies demonstrate the pleiotropic effects of fibrates. Except lowering plasma lipid levels they can influence blood coagulation abnormalities and stabilise atherosclerotic lesions--a frequent result of the activation of inflammatory cells within the vascular wall. The anti-inflammatory action of fibrates includes inhibiting the release of many cytokines, such as Tumor Necrosis Factor e (TNF-alpha) by these cells. The aim of this study was to evaluate the effect of fenofibrate on the plasma levels of Plasminogen Activator Inhibitor type 1 (PAI-1) and fibrinogen in patients with combined dyslipidemia. Moreover, we assessed the amount of TNF-alpha released by peripheral blood isolated monocytes before and after therapy. Fourteen patients (8 women and 6 men) with hyperlipidemia IIb were treated with micronized fenofibrate (Lipanthyl 200 m, Fournier) in a daily dose of 200 mg for one month. The control group consisted of 12 individuals matched for age with biochemical confirmation of normolipemia. Plasma PAI-1 and TNF-alpha levels were measured by the ELISA method. Fibrinogen levels were measured according to the commonly used Clauss method. Before treatment the haemostatic compounds and TNF-alpha studied were significantly higher in the group with hyperlipidaemia IIb compared to the control group. One-month therapy with fenofibrate resulted in significant decrease of triglycerides and total cholesterol. After treatment, PAI-1 and fibrinogen levels also decreased significantly: PAI-1 from 101.18 +/- 9.74 ng/mL to 81.22 +/- 6.68 ng/mL, p < 0.01 and fibrinogen from 364.5 +/- 29.6 mg/dL to 294.7 +/- 19.3 mg/dL, p < 0.01. The study also revealed that the level of produced TNF-alpha decreased significantly from 2136.0 +/- 250.8 pg/mL to 1336.8 +/- 132.0 pg/mL, p < 0.05. These results may confirm new pathways of fibrates action.

Adult↗

PubMedDate not supplied

Progress in pharmacotherapy of thrombosis.

Excessive coagulation and impaired fibrinolysis lead to many hemostatic disorders, which enhance the risk of development of life-threatening cardiovascular diseases such as myocardial infarction, stroke, deep venous thrombosis and pulmonary embolism, belonging to the most important factors influencing morbidity and mortality in civilized societies. The adverse events induced by currently used drugs, the need for regular monitoring of coagulation parameters, inconvenient, in some cases, route of administration stimulate further search for novel, effective and safe methods of therapies of these disorders. In this paper, we describe those new agents which are now under experimental and clinical study, such us prostanoids, nitroaspirin, GP IIb/IIIa receptor antagonists, thienopyridine derivatives, collagen-GPVI and von Willebrand factor-GPIb-IX contact blockers, direct thrombin inhibitors, inhibitors of thrombin-platelet interactions, factor VII inhibitors and tissue factor-factor VII contact blockers. Based on the available literature, we discuss the possible role of these agents in the future prevention and treatment of thromboembolic diseases.

Animals↗

PubMedDate not supplied

Immunophilin ligands decrease release of pro-inflammatory cytokines (IL-1beta, TNF-alpha and IL-2 in rat astrocyte cultures exposed to simulated ischemia in vitro.

The aim of present study was to evaluate the effects of immunophilin ligands (cyclosporin A, FK506 and rapamycin) on the simulated ischemia-induced release of pro-inflammatory cytokines (IL-1beta, TNF-alpha and IL-2) in rat primary astrocyte cell cultures. Astrocytes were exposed to cyclosporin A (CsA) (0.25, 0.5, 1, 10, 20 and 50 microM), FK506 (1, 10, 100, 1000 nM) and rapamycin (10, 100, 500 and 1000 nM). In vitro simulated ischemia significantly increased secretion of IL-1beta, TNF-alpha and IL-2 by astrocyte cultures deprived of microglia (by shaking and incubating with L-leucine methyl ester). CsA (at concentrations of 10-50 microM), FK506 (at all used concentrations) and rapamycin (in dose-dependent manner) significantly attenuated IL-1beta release after 24 h exposure to ischemic conditions. Immunophilin ligands at all used concentrations significantly decreased TNF-alpha levels in culture media after 24 h exposure to ischemia. Moreover, significant decrease in IL-2 secretion at 0.25, 0.5, 1 and 50 microM CsA and FK506 at concentrations of 100 and 1000 nM were observed. The results suggest that immunophilin ligands may regulate glial activity during ischemia by affecting the release of pro-inflammatory cytokines.

Animals↗

PubMedDate not supplied

Effect of simvastatin and fluvastatin on plasma fibrinogen levels in patients with primary hypercholesterolemia.

The aim of the study was to compare the effect of treatment with two different statins on plasma fibrinogen levels in patients with primary isolated hypercholesterolemia. Sixty three patients enrolled into the study were randomly divided into two groups, treated with simvastatin (20 mg/d) or fluvastatin (40 mg/d), respectively. Plasma lipid profile and fibrinogen levels were measured after 4 and 12 weeks of the therapy. Both drugs decreased total and LDL cholesterol and apoprotein B levels. Simvastatin additionally reduced triglyceride levels. After 4 weeks of treatment both drugs tended to increase plasma fibrinogen levels, while after 12 weeks fibrinogen level was significantly increased in the simvastatin-treated patients. The effect on fibrinogen did not correlate with their lipid-lowering potential, gender and was similar in patients positive and negative for anti-Helicobacter pylori or anti-Chlamydia pneumoniae antibodies. Our results support the findings about a relatively weak effect of statin therapy on plasma fibrinogen level and partially explain contradictory results of previous studies.

Adult↗

PubMedDate not supplied

Influence of antidepressant drugs on macrophage cytotoxic activity in rats.

The aim of the study was to evaluate the in vivo and in vitro effects of antidepressant drugs on cytotoxic activity of rat spleen macrophages. In the in vivo experiment, rats were injected subcutaneously with two different doses (2 or 10 mg/kg) of desipramine, fluvoxamine and fluoxetine. The drugs were given once, for 2, 4 or 8 weeks. In the in vitro experiment, spleen macrophages were cultured with three different concentrations of desipramine (3.75, 0.75, or 0.075 mM), fluvoxamine (3.14, 0.62, or 0.062 mM), and fluoxetine (3.23, 0.64, or 0.064 mM) for 72 h. The cytotoxic activity of macrophages was evaluated by measuring the lysis of ((51)Cr) chromate-labelled P-815 target cells. In the in vivo experiment, a single dose of fluvoxamine (2 and 10 mg/kg) and fluoxetine (10 mg/kg) significantly decreased macrophage cytotoxic activity. Fluvoxamine (2 and 10 mg/kg), fluoxetine (10 mg/kg) and desipramine (10 mg/kg) administrated for 14 days also decreased macrophage cytotoxic activity. Twenty-eight day treatment with desipramine (2 and 10 mg/kg) decreased macrophage cytotoxic activity. Desipramine, fluvoxamine and fluoxetine given for 56 days did not affect macrophage cytotoxic activity. In the in vitro experiment, antidepressant drugs did not affect the cytotoxic activity of macrophages. The results of the study indicate that the effects of antidepressant drugs on macrophage cytotoxic activity depend on the drug type, dose and duration of the treatment.

Animals↗

PubMedDate not supplied

Amphetamine-induced effects on neuropeptide Y in the rat brain.

Repeated (+)-amphetamine sulfate (AMPH) administration (5 mg/kg sc twice daily for 6 days and once on day 7) markedly and reversibly decreased (until 96 h after the final dose) neuropeptide Y-like immunoreactivity (NPY-LI) in the rat striatum (caudate-putamen) and nucleus accumbens, and had no effect on NPY-LI in the hippocampus. No significant alterations were detected in the hybridization signal of NPY mRNA4 and 24 h after the end of AMPH treatment. A single dose of AMPH (5 mg/kg sc) administered to rats 4 and 24 h prior to sacrifice had no effect on NPY-LI in the brain structures studied. Moreover, AMPH injected 8 days after the last dose of repeated AMPH administration did not change NPY-LI up to 72 h. The minimal dose of haloperidol, the strong mixed dopaminergic D2/D1 receptor antagonist, (0.75 mg/kg injected ip 30 min before each of the multiple AMPH administrations) that was sufficient to completely block stereotypy and hyperlocomotion elicited by multiple AMPH administrations enhanced the AMPH-induced decrease in the striatal and accumbens NPY-LI. Our results suggest that NPY neurons in the striatum, nucleus accumbens and hippocampus are not directly involved in the acute behavioral response to AMPH (stereotypy and hyperlocomotion) as well as in the initiation and expression of AMPH-induced behavioral sensitization.

Amphetamine↗