Finasteride Has Regionally Different Effects on Brain Oxidative Stress and Acetylcholinesterase Activity in Acute Thioacetamide-Induced Hepatic Encephalopathy in Rats

Finasteride (FIN) inhibits neurosteroid synthesis and potentially improves the course of hepatic encephalopathy (HE). This study aimed to investigate the effects of FIN on brain oxidative stress and acetylcholinesterase (AchE) activity in acute thioacetamide-induced HE in rats. Male Wistar rats were divided into groups: 1. control; 2. thioacetamide-treated group (TAA; 900 mg/kg); 3. finasteride-treated group (FIN; 150 mg/kg); 4. group treated with FIN and TAA (FIN+TAA). Daily doses of FIN (50 mg/kg) and TAA (300 mg/kg) were administered intraperitoneally during three days and in FIN+TAA group FIN was administered 2h before every dose of TAA. FIN pretreatment prevented TAA-induced rise in malondialdehyde level in the cortex due to restoration of catalase activity and increased expression of superoxide dismutase 1 (SOD1) and induced an increase in malondialdehyde level in the thalamus due to reduction of glutathione peroxidase (GPx) and glutathione reductase (GR) activity. Although FIN pretreatment did not affect malondialdehyde level in hippocampus and caudate nucleus, hippocampal SOD1 expression was higher (p<0.05) and GR activity lower in FIN+TAA vs. TAA group (p<0.05). GPx activity was lower in caudate nucleus in FIN+TAA vs. TAA group (p<0.01). FIN pretreatment prevented TAA-induced rise in AchE activity in the thalamus and caudate nucleus and AchE activity correlates inversely in the thalamus (p<0.05) and positively in caudate nucleus (p<0.01) with malondialdehyde level. FIN has regionally selective effects on oxidative stress and AchE activity in the brain in acute TAA-induced HE in rats. The prooxidant role of FIN in the thalamus may be causally linked with inhibition of AchE.     

Assessment of the protective and therapeutic effect of melatonin against thioacetamide‐induced acute liver damage

Acute or chronic damage to the liver may occur through alcohol, drugs, viruses, genetic disorders, and toxicity. In this study, we planned to investigate the protective and therapeutic effects of melatonin (Mel) by causing damage to the liver with thioacetamide (TAA). Thirty‐five rats were used. Group I: control group (seven pieces), group II: Mel group (seven pieces) the single dose on the first day of the experiment was 10 mg/kg, group III: TAA (seven pieces) 300 mg/kg with 24‐hour intervals, two doses, group IV: Mel + TAA group (seven pieces) 10 mg/kg single dose Mel was applied 24 hours before TAA application, group V: TAA + Mel group (seven pieces) single dose (24th hour) of 10 mg/kg Mel was administered after TAA (300 mg/kg) two doses. The liver histology was evaluated. Apoptosis, autophagy, and necrosis markers in tissue were determined by immunohistochemistry. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) levels in blood serum samples and transforming growth factor‐β (TGF‐β) and tumor necrosis factor‐α (TNF‐α) levels were determined in liver tissue. TAA affected histologically the classical lobule structure both in cell cords and sinusoids. Caspase‐3, RIP3, and LC3 levels were increased in group III compared with the control group. TAA did not cause a statistically significant change in TNF‐α level but decreased the TGF‐β level significantly. AST and ALT levels were statistically significant in group II and V compared with group I, the ALP level was significant in group IV compared with group II. The results of this study showed that TAA caused significant damage to tissues and increased cell death, Mel was found to have more therapeutic than the protective effect on tissues.     

Effects of shark hepatic stimulator substance on the function and antioxidant capacity of liver mitochondria in an animal model of acute liver injury

This study was carried out to investigate whether shark hepatic stimulator substance （HSS） can prevent acute liver injury and affect mitochondrial function and antioxidant defenses in a rat model of thioacetamide （TAA）-induced liver injury. The acute liver injury was induced by two intraperitoneal injections of TAA （400 mg/kg） in a 24 h interval. In the TAA plus shark HSS group, rats were treated with shark HSS （80 mg/kg） 1 h prior to each TAA injection. In this group, serum liver enzyme activities were significantly lower than those in the TAA group. The mitochondrial respiratory control ratio was improved, and the mitochondrial respiratory enzyme activities were increased in the TAA plus shark HSS group. The mitochondrial antioxidant enzyme activities and glutathione level were higher in the TAA plus shark HSS group than in the TAA group. These results suggest that the protective effect of shark HSS against TAA-induced acute liver injury may be a result of the restoration of the mitochondrial respiratory function and antioxidant defenses and decreased oxygen stress.     

Age-related increased susceptibility of male Fischer 344 rats to acetaminophen nephrotoxicity

Male Fischer 344 rats classified as young (2-4 months), middle-aged (12-14 months) and aged (22-25 months) received 300, 600 or 800 mg/kg acetaminophen (APAP) intraperitoneally and were sacrificed 24 hr later. Blood urea nitrogen (BUN) concentration and urinary glucose and osmolality were determined. In addition, kidneys were evaluated for histopathological changes. APAP did not affect osmolality or BUN concentrations and failed to produce lesions after any dose in young rats. Osmolality was decreased 40% and 50% in middle-aged and aged rats, respectively, after 800 mg/kg APAP. Glucosuria was prominent in aged rats after the 600 and 800 mg/kg doses were administered, while middle-aged rats showed little glucosuria after these doses. BUN concentrations were elevated 89% and 183% in middle-aged and aged rats, respectively, given 600 mg/kg APAP; after 800 mg/kg, BUN concentrations were elevated approximately four-fold in both age groups. Pathological evaluations showed a greater incidence of acute tubular necrosis (ATN) in aged kidneys compared to kidneys of middle-aged rats after 600 mg/kg, while the two older groups exhibited similar, more severe ATN after 800 mg/kg APAP. These data suggest an age-related increased susceptibility of male Fisher 344 rats to APAP nephrotoxicity.     

Activity of the human carcinogens benzidine and 2-naphthylamine in triple- and single-dose mouse bone marrow micronucleus assays: results for a combined test protocol

The activities of the human bladder carcinogens benzidine and 2-naphthylamine in the mouse bone marrow micronucleus assays using a limited test protocol (oral dosing to male mice, sampling 24 h later) have recently been established. As a contribution to the International Collaborative Study on the evaluation of the sensitivity of the triple-dose micronucleus test protocol it was decided to re-evaluate benzidine and 2-naphthylamine using a combined triple- and single-dose test protocol. Benzidine gave a clear positive response in male mice 24 h after 3 daily doses of 150 and 300 mg/kg. A single dose of 900 mg/kg of benzidine gave a weaker response 24 h after dosing. In the case of 2-naphthylamine a stronger positive response was observed 24 h after a single dose of 600 mg/kg as compared to 3 daily doses of 200 or 400 mg/kg. There was no significant difference in the increased positive response observed for a single dose of 30 mg/kg of cyclophosphamide compared with 3 successive daily doses of 10 mg/kg. Based on the present data the combined triple/single-dose micronucleus test protocol is strongly supported.     

Effect of Dietary Nickel Chloride on Splenic Immune Function in Broilers

This study was designed to evaluate the effects of dietary nickel chloride (NiCl₂) on the splenic immunity in broilers by observing changes of cytokine mRNA expression and protein levels, immunoglobulin (IgA, IgG, and IgM) contents, and IgA⁺ B cell and T-cell numbers using the methods of qRT-PCR, flow cytometry (FCM), and ELISA. A total of 240 1-day-old avian broilers were equally allocated into four groups and fed on a corn–soybean basal diet as the control diet or the same diet supplemented with 300, 600, and 900 mg/kg NiCl₂ for 42 days. The mRNA expression and protein levels of IL-2, IL-6, IL-10, IL-12, TNF-α/LITAF, IFN-γ, and IgA, IgG, and IgM contents were significantly decreased (p?<?0.05 or p?<?0.01) in the 300-, 600-, and 900-mg/kg NiCl₂ groups when compared with those of the control group, which was consistent with the reduction of T-cell subset percentages and IgA⁺ B cell numbers in the 300-, 600-, and 900-mg/kg NiCl₂ groups. The abovementioned results showed that dietary NiCl₂ in excess of 300 mg/kg caused damage on splenocytes and splenic immune function. The results of the present study provided new experimental evidences for further study on the effect mechanism of NiCl₂ on splenic immunity.     

Effects of L-arginine on prevention and treatment of lithium-pilocarpine-induced status epilepticus

The effects of various doses of L-arginine, a nitric oxide substrate, on lithium-pilocarpine-induced seizures were studied in rats. Rats were implanted with chronic, stainless steel screw electrodes epidurally for electrocortical recordings. A control group received 3 mEq/kg LiCl (i.p.) and 24 h later 45 mg/kg pilocarpine HCl (i.p.). Two different experimental procedures were followed: (1) L-arginine was applied in doses of 100 mg/kg, 300 mg/kg or 500 mg/kg (i.p.), 30 min before pilocarpine injection; (2) 300 mg/kg, 500 mg/kg or 1000 mg/kg (i.p.) L-arginine was injected either 5 min or 30 min after the onset of status epilepticus (SE). L-arginine (300 mg/kg) injected 30 min before pilocarpine significantly reduced the percentage of SE, but did not change the latency to SE or 24-hour survival. These parameters were not significantly affected by the 100 mg/kg or 500 mg/kg dose of L-arginine. On the other hand, no dose of L-arginine that was applied after SE had begun, had any significant influence on the seizures. We concluded that L-arginine may prevent seizure activity in some but not all doses, and does not have any effect on the ongoing seizure activity.     

Changes of the Serum Cytokine Contents in Broilers Fed on Diets Supplemented with Nickel Chloride

Cytokines are immunoregulatory proteins which play an important role in the immune system. The purpose of this study was to examine the serum cytokine contents including interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), interferon gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α) induced by dietary nickel chloride in broilers by enzyme-linked immunospecific assay. A total of 240 one-day-old avian broilers were divided into four groups and fed on a corn–soybean basal diet as control diet or the same basal diet supplemented with 300, 600, and 900 mg/kg of nickel chloride. During the experimental period of 42 days, the results showed that the serum IL-2, IL-4, IL-6, IL-10, IFN-γ and TNF-α contents were lower (p?<?0.05 or p?<?0.01) in the 300, 600, 900 mg/kg groups than those in the control group. It was concluded that dietary nickel chloride in the range of 300 to 900 mg/kg could reduce the serum cytokine contents, which could finally impact the immune function in broilers.     

Effects of Nickel Chloride on the Erythrocytes and Erythrocyte Immune Adherence Function in Broilers

This study was conducted to investigate the immune adherence function of erythrocytes and erythrocyte induced by dietary nickel chloride (NiCl₂) in broilers fed on a control diet and three experimental diets supplemented with 300, 600, and 900 mg/kg NiCl₂ for 42 days. Blood samples were collected from five broilers in each group at 14, 28, and 42 days of age. Changes of erythrocyte parameters showed that total erythrocyte count (TEC), hemoglobin (Hb) contents, and packed cell volume (PCV) were significantly lower (p?p?p?p?+/K⁺-ATPase) and calcium adenosine triphosphatase (Ca²⁺-ATPase) activities were significantly decreased (p?p?2-treated groups. The results of erythrocyte immune adherence function indicated that erythrocyte C_3b receptor rosette rate (E-C_3bRR) was significantly decreased (p?p?p?p?2 in excess of 300 mg/kg caused anemia and impaired the erythrocytic integrity, erythrocytic ability to transport oxygen, and erythrocyte immune adherence function in broilers. Impairment of the erythrocytes and erythrocyte immune adherence function was one of main effect mechanisms of NiCl₂ on the blood function.     

Citrus medica L. cv Diamante (Rutaceae) peel extract improves glycaemic status of Zucker diabetic fatty (ZDF) rats and protects against oxidative stress

This study aimed to investigate the antidiabetic, antilipidaemic and antioxidant activities of Citrus medica cv Diamante (Rutaceae) hydroalcoholic (CD) peel extract in Zucker diabetic fatty (ZDF) rats. The ability of CD to protect against oxidative stress was investigated by using different in vitro assays and in vivo by using the reactive oxygen metabolites-derived compounds (d-ROMs) test and the biological antioxidant potential test (BAP). Two different doses of CD extract (300 and 600?mg/kg/die) were administered at ZDF rats for 4 weeks. CD reduced cholesterol and triglycerides levels. A dose-dependent effect on body weight and serum glucose levels was observed. A decrease of d-ROMs and an increase of BAP were recorded by using the dose of 600?mg/kg. The extract inhibited lipid peroxidation (IC₅₀ value of 0.23?mg/ml). These findings suggest as an efficient phytotherapeutic approach in combating hyperlipidaemic and hyperglycaemic disorders.     

Neuroprotective properties of aucubin in diabetic rats and diabetic encephalopathy rats

In this study, we determined the neuroprotective effect of aucubin on diabetes and diabetic encephalopathy. With the exception of the control group, all rats received intraperitoneal injections of streptozotocin (STZ; 60?mg/kg) to induce type 1 diabetes mellitus (DM). Aucubin (1, 5, 10?mg/kg ip) was used after induction of DM (immediately) and diabetic encephalopathy (65?days after the induction of diabetes). The diabetic encephalopathy treatment groups were divided into short-term and long-term treatment groups. Treatment responses to all parameters were examined (body weight, plasma glucose, Y-maze error rates and proportion of apoptotic cells). In diabetic rats, aucubin controlled blood glucose levels effectively, prevented complications, and improved the quality of life of diabetic rats. In diabetic encephalopathy, aucubin significantly rescued neurons in the hippocampal CA1 subfield and reduced working errors during behavioral testing. The significant neuroprotective effect of aucubin could be seen not only in the short term (15?days) but also in the long term (45?days), which was a highly encouraging finding. These data suggest that aucubin may be a potential neuroprotective agent.     

Protective effect of L-citrulline against acute gastric mucosal lesions induced by ischemia-reperfusion in rats

The present study investigated the protective effect of L-citrulline on gastric mucosal injury induced by ischemia-reperfusion (IR) in rats. Under anesthesia, the celiac artery was clamped for 30 min, and then the clamp was removed for 60 min reperfusion. Sixty minutes before ischemia, L-citrulline was administered intragastrically at doses of 300, 600, and 900 mg/kg. After the experiment, the stomachs were removed for biochemical and histological examinations. Pretreatment with L-citrulline (300, 600, and 900 mg/kg) significantly ameliorated the gastric damage caused by IR. Moreover, L-citrulline prevented the production of lipid peroxidation and inhibited the increase of myeloperoxidase activity. The elevation in total nitric oxide synthase (NOS) activity, inducible NOS activity, and inducible NOS protein expression as well as the decrease in constitutive NOS activity and gastric mucus level in the gastric mucosa induced by IR were significantly prevented. However, the protective effect mediated by L-citrulline was significantly antagonized by coadministration of L-nitroarginine methyl ester (10 mg/kg, s.c.). These results suggest that part of the mechanism of gastric protection by L-citrulline might be through inhibiting neutrophil infiltration and preserving gastric mucus synthesis and secretion in rats, functions that are closely related to the maintenance of constitutive NOS activity.     

Antinociceptive activity of methanolic extract of leaves of Achyranthes aspera Linn. (Amaranthaceae) in animal models of nociception

Antinociceptive activity of methanolic extract of leaves of A. aspera was studied by peripheral/non-narcotic model of nociception like acetic acid induced writhing syndrome test and central/narcotic models like hot plate and tail flick tests. The methanolic extract of the plant, administered orally (@ 300, 600 and 900 mg/kg, body weight) and the standard drug (piroxicam; 10 mg/kg body weight, po) produced significant analgesic activity in acetic acid induced writhing syndrome as compared to the vehicle treated control group. In the hot plate analgesic test, in A. aspera at the above doses and the standard drug treated group (morphine sulphate @ 1.5 mg/kg, ip), the duration of reaction time (sec) increased dose dependently and significantly compared to the control group. In the tail flick test, the plant extract produced dose dependant increase in reaction time which was significantly higher in the test and standard group compared to the control group. The plant possesses significant antinociceptive property as evidenced in all the animal models of nociception. It might possibly exert its effect through diverse mechanism that may involve both central and peripheral pathways. The preliminary phytochemical investigation revealed the presence of steroids, alkaloids and triterpene in the methanolic extract of leaves of A. aspera which may be responsible for its antinociceptive activity.     

Does vigabatrin possess an anticonvulsant action against pentylenetetrazol-induced seizures in developing rats?

Anticonvulsant action of vigabatrin (300, 600, 900 and/or 1200 mg/kg i.p.), an inhibitor of GABA-transaminase, was studied in a model of motor sezures elicited by pentylenetetrazol. Five age groups of rats (7, 12, 18, 25 and 90 days old) received a s.c. injection of pentylenetetrazol 4, 6 and/or 24 hours after vigabatrin administration. The incidence of minimal, predominantly clonic seizures was not changed in any age group, but their latencies were prolonged in 18- and 25-day-old rats. Generalized tonic-clonic seizures were influenced in a more complex manner. Incidence of these seizures was decreased in 7-day-old rat pups 24 hours after vigabatrin administration. Higher doses of vigabatrin exhibited a similar effect in adult rats at all intervals studied. Specific suppression or at least restriction of the tonic phase was observed in all groups of immature rats, the effect was more marked 24 hours after vigabatrin than at shorter intervals. The anticonvulsant action of vigabatrin, which could be demonstrated mainly against generalized tonic-clonic seizures, varies markedly during development.     

Acute administration of levetiracetam in tonic pain model modulates gene expression of 5HT1A and 5HT7 receptors in the thalamus of rats (Rattus norvergicus)

The nociceptive effect of Levetiracetam (LEV) on the expression of 5-HT_1A and 5-HT₇ receptors found in the thalamus was evaluated. Thirty-six male rats (Wistar) were randomized into six groups: in the Control group without treatment; LEV50 group LEV was administered in a single dose of 50 mg/kg i.g.; in the LEV300 group LEV dose of 300 mg/kg i.g.; in the FORMALIN group the formalin test was performed; in the LEV50/FORMALIN group LEV dose of 50 mg/kg i.g and the formalin test was performed; in the LEV300/FORMALIN group LEV dose of 300 mg/kg i.g and the formalin test was performed, subsequently the thalamus was dissected in all groups. In the formalin tests LEV exhibited an antinociceptive effect in the LEV300/FORMALIN group (p?<?0.05) and a pronociceptive effect in the LEV50/FORMALIN group (p?<?0.001). The results obtained by Real-time PCR confirmed the expression of the 5-HT_1A and 5-HT₇ receptors in the thalamus, 5-HT_1A receptors increased significantly in the FORMALIN group and the LEV300/FORMALIN group (p?<?0.05). 5-HT7 receptors are only over expressed at a dose of 300 mg/Kg of LEV with formalin (p?<?0.05). This suggests that LEV modulates the sensation of pain by controlling the expression of 5-HT_1A and 5-HT₇ in a tonic pain model, and that changes in the expression of 5-HT_1A and 5-HT₇ receptors are associated with the sensation of pain, furthermore its possibility to be used in clinical treatments for pain.

     

Dose-dependent effects of carbendazim on rat thymus

In this study, the effects of carbendazim on the thymus in male rats were evaluated. Carbendazim was administered at 0, 150, 300 and 600 mg kg(-1) day(-1) doses by gavage to male rats for 15 weeks. Body weights of rats in all groups were recorded weekly during treatment. At the end of the experiment, the effects of carbendazim on the thymus were investigated histopathologically and morphologically. Also, based on these effects, change in immunolocalization of fibronectin (FN), which is a component of the extracellular matrix, was investigated immunohistochemically. Fibrosis and oedema were observed in the thymus of rats treated with 300 and 600 mg kg(-1) day(-1) doses of carbendazim. Also in this region, an increase in FN density was noted at the end of the immunohistochemical investigation. A decrease was observed in absolute and relative thymus weights of rats treated with carbendazim compared with the control group. While the decrease in absolute thymus weight was statistically significant in rats exposed to carbendazim at the highest dose, the decrease in relative thymus weights was statistically significant for all carbendazim doses.     

Downregulation of TLR4 and 7 mRNA Expression Levels in Broiler’s Spleen Caused by Diets Supplemented with Nickel Chloride

Toll-like receptors (TLRs) are important immune receptors in discriminating self from nonself and in initiating the innate and adaptive immune response. TLR4 and TLR7 have been proven to be highly expressed in chicken’s spleen. Thus, this study was to evaluate the TLR4 and TLR7 messenger RNA (mRNA) expression levels in the spleen of broilers fed diets supplemented with nickel chloride (NiCl₂) using the methods of quantitative real-time PCR (qRT-PCR). Two hundred forty-one-day-old avian broilers were equally divided into 4 groups and fed on a corn-soybean basal diet as control diet or the same basal diet supplemented with 300, 600, and 900 mg/kg of NiCl₂ for 42 days. Results showed that TLR4 and TLR7 mRNA expression levels in the spleen were lower (P?<?0.05 or P?<?0.01) in the 300, 600, and 900 mg/kg groups than those in the control group. It was concluded that dietary NiCl₂ in excess of 300 mg/kg could lower TLR4 and TLR7 mRNA expression levels in the spleen of broilers, implying that NiCl₂ could impair the innate and adaptive immunity in spleen by injuring immunocytes and/or decreasing the content of cytokines through TLRs.     

Moringa peregrina leaf extracts produce anti-obesity,hypoglycemic, anti-hyperlipidemic,and hepatoprotective effects on high-fat diet fed rats

This present research investigated the anti-obesity and hepatoprotective effects of ethanolic Moringa peregrina leaf (MPLE) and bark extracts (MPBE), in the rats fed with a high-fat diet (HFD). Healthy male rats (n = 48) were randomly distributed to six groups (n = 8): control AIN-93 diet; HFD; HFD + MPBE bark extracts ((300 mg/kg); HFD + MPBE (600 mg/kg); HFD + MPLE (300 mg/kg); HFD + MPLE (600 mg/kg). HFD-fed rats in the Moringa peregrina (MP) treatment groups received orally administered MP leaf or bark extract daily for eight weeks. The results revealed that both doses of MP leaf extract significantly reduced HFD-induced increases in their food intake and the gained body weight, fat pad weights (visceral, subcutaneous, and epididymal), glucose and insulin plasma levels, and leptin and resistin serum levels in HFD-fed rats. Concomitantly, MP leaf extract improved glucose levels after oral or intraperitoneal glucose tolerance tests, reduced serum cholesterol, triglycerides, and the low-density lipoprotein LDL concentration, reduced hepatic triglycerides and cholesterol levels, and increased serum high-density lipoproteins HDL levels and triglycerides and cholesterol levels in fecal. Moreover, the administration of MPLE to HFD-fed rats improved liver architecture, reduced fat accumulation, reduced hepatic malondialdehyde, tumor necrosis factor-α, and interleukin-6 levels. Hepatic glutathione peroxidase, superoxide dismutase, and catalase activities were significantly increased. All observed effects were more pronounced in HFD-fed rats treated with a 600 mg/kg MP dose. However, neither dose of MPBE altered the measured markers in the HFD-fed rats. In conclusion, MPLE showed potential anti-obesity and hepatoprotective activity in HFD-induced obese rats, mediated by reduced lipid absorption, anti-hyperlipidemic effects, and hepatic antioxidant effects.     

Role of carnosine in preventing thioacetamide-induced liver injury in the rat

Carnosine (beta-alanyl-L-histidine) is a dipeptide with antioxidant properties. Free radicals are involved in the pathogenesis of acute liver injury induced by thioacetamide (TAA). In this study, we investigated the effect of carnosine treatment on TAA-induced oxidative stress and hepatotoxicity. Rats were injected intraperitoneally with TAA (500 mg/kg) and carnosine (250 mg/kg, intraperitoneal) was co-administered with TAA. All animals were killed 24 h after injections. TAA administration resulted in hepatic necrosis, significant increases in plasma transaminase activities as well as hepatic lipid peroxide levels. In addition, hepatic antioxidant system was found to be depressed following TAA administration. When carnosine was co-administered with TAA in rats, plasma transaminase activities were found to approach to normal values in rats. Histological findings also suggested that carnosine has preventive effect on TAA-induced hepatic necrosis. Carnosine treatment caused significant decreases in lipid peroxide levels in TAA-treated rats without any changes in enzymatic and non-enzymatic antioxidants except vitamin E in the liver of rats. Our findings indicate that carnosine, in vivo may have a preventive effect on TAA-induced oxidative stress and hepatotoxicity by acting as an non-enzymatic antioxidant itself.     

Enhanced prolactin inhibition following chronic treatment with haloperidol and morphine

Withdrawal from chronic haloperidol or morphine treatment resulted in lower circulating levels of serum prolactin in male rats. A low dose of apomorphine (0.32 mg/kg), which had no effect on serum prolactin in untreated rats, diminished serum prolactin in the treated rats. A lower dose of apomorphine (0.08 mg/kg) also ineffective in control rats, elevated serum prolactin in the treated rats.