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Antiretroviral therapy has revolutionized the treatment of the human immunodeficiency virus because it has improved the clinical outcomes of patients. It is essential that these drugs cross the blood-brain barrier, since the virus is present in the central nervous system (CNS). Efavirenz passes through this barrier satisfactorily and can reduce the deleterious central effects of the human immunodeficiency virus. However, patients treated with efavirenz have been observed to experience psychiatric symptoms such as mania, depression, suicidal thoughts, psychosis, and hallucinations. The aim of this review is to describe the pharmacokinetic and pharmacodynamic properties of efavirenz and its major neuropsychiatric symptoms and the neurochemical pathways associated with these changes in the CNS. The databases Medline and Lilacs were used to search for review articles and preclinical and clinical research articles published from January 1996 to 2010. The search terms used were efavirenz, central nervous system, neuropsychiatry, neurotransmitters, adverse effects, and neurochemistry. Subject categories considered included effects on viral replication, pharmacokinetic and pharmacodynamic properties of efavirenz, and neuropsychiatric adverse effects including time course, duration, and probable mechanisms involved. The mechanisms involved in these changes include interference with cytochrome P450 enzymes, cytokines, tryptophan-2-3-dioxygenase, and brain creatine kinase.

This study assesses the antinociceptive effect induced by different dosages of topiramate (TP), an anticonvulsant drug that is orally administered in models of neuropathic pain and acute pain in rats and mice, respectively. Orally administered TP (80 mg/Kg) in mice causes antinociception in the first and second phases of a formalin test, while in doses of 20 and 40 mg/Kg it was only effective in the second phase. TP (80 mg/Kg, p.o) also exhibited antinociceptive action in the hot plate test, however, it did not have an effect in the capsaicin test in mice, nor in the model of neuropathic pain in diabetic rats. The antinociceptive effect caused by TP (80 mg/Kg, p.o) in the formalin test was reversed by prior treatment with naloxone (opioid antagonist), but not with glibenclamide (antagonist of the potassium channel), ondansetron (antagonist of the serotonin 5HT3 receptor) or cyproheptadine (antagonist of the serotonin 5HT2A receptor).The data show that TP has an important antinociceptive effect in the models of nociception induced by chemical (formalin) or thermal (hot plate) stimuli, and that the opioid system plays a part in the antinociceptive effect, as shown by formalin.

Status epilepticus (SE) is clinically defined as prolonged electrical and clinical seizure activity in which the patient does not regain consciousness to a normal alert state between repeated tonic-clonic attacks. The disorder is a neurological emergency associated with a mortality rate of 10-12% and an even greater morbidity. SE can lead to permanent pathological damage and altered physiological function in certain brain regions and induces major changes in membrane phospholipids, massive increases in arachidonic acid concentrations, diacylglycerol-mediated activation, of protein kinase C, calcium-mediated changes in calmodulin kinase II and possibly generation of free radicals that could play an essential role in the mechanism of oxidative stress involved in neural damage. SE can be characterized by a permanent change in neurotransmitter systems and oxidative stress that it is more facilitated in the brain rather than in other tissues because it contains large quantities of oxidizable lipids and metals. The role of monoamines, amino acid and oxidative stress in pilocarpine- induced SE will be investigated in hippocampus, striatum and frontal cortex of adult rats. The SE studied will be induced by pilocarpine (400mg/kg, s.c.) and the results observed were investigated during acute phase. The data obtained suggests that pilocarpine induced amino acid and oxidative stress changes in brain regions that are similar to the one verified in human temporal lobe epilepsy.

The mechanism underlying the vulnerability of the brain to status epilepticus (SE) induced by pilocarpine remains unknown. Oxidative stress has been implicated in a variety of acute and chronic neurologic conditions, including SE. The present study was aimed at was investigating the changes in catalase activity after pilocarpine-induced seizures and SE. The Control group was treated with 0.9% saline (NaCl, subcutaneously (s.c.)) and sacrificed 1 h after the treatment. Another group was treated with pilocarpine (400 mg/kg, s.c., Pilocarpine group) and sacrificed 1 h after treatment. The catalase activity in the cerebellum, hippocampus, frontal cortex and striatum of Wistar rats was determined. The results have shown that pilocarpine administration and resulting SE produced a significant increase in the catalase activity in the hippocampus (36%), striatum (31%) and frontal cortex (15%) of treated adult rats. Nevertheless, in the adult rat cerebellum after SE induced by pilocarpine no change was observed in the catalase activity. Our results demonstrated a direct evidence of an increase in the activity of the scavenging enzyme (catalase) in different cerebral structures during seizure activity that could be responsible for eliminating oxygen free radicals and might be one of the compensatory mechanisms to avoid the development of oxidative stress during the establishment of SE induced by pilocarpine. Our reports also indicate clear regional differences in the catalase activity caused by pilocarpine-induced seizures and SE and the hippocampus might be the principal area affected and cerebellum does not modify for this parameter studied during epileptic activity.

The aim of the study was to investigate the lipid peroxidation levels, nitrite formation, GABAergic and glutamatergic receptor densities in the hippocampus, frontal cortex and striatum of Wistar rats after seizures and status epilepticus (SE) induced by pilocarpine. The control group was treated with 0.9% saline and sacrificed 1 h after the treatment. One group of rats was administered with pilocarpine (400 mg/kg sc) and sacrificed 1 h after treatment. The result shows that pilocarpine administration and the resulting SE produced a significant increase of lipid peroxidation level in the hippocampus (46%), striatum (25%) and frontal cortex (21%). In nitrite formation, increases of 49%, 49% and 75% in hippocampus, striatum and frontal cortex, respectively, was observed. Pilocarpine treatment induced down-regulation of GABAergic receptors in the hippocampus (38%), striatum (15%) and frontal cortex (11%). However, with regard to glutamatergic receptor densities, increases in the hippocampus (11%), striatum (17%) and frontal cortex (14%) was observed during the observation period. These results show a direct evidence of lipid peroxidation and nitrite formation during seizure activity that could be responsible for the GABAergic and glutamatergic receptor concentration changes during the estabilishment of SE induced by pilocarpine.

Seizures and death are the more important toxic consequences related to cocaine overdose. Some reports have shown that pharmacological manipulations in dopaminergic, serotonergic and noradrenergic systems alter the occurrence of cocaine-induced convulsions and death. Based on this fact, this work was performed to determine the changes in monoamine levels (DA, 5-HT and NE) and their metabolites (DOPAC, HVA and 5-HIAA) after cocaine-induced status epilepticus (SE) and death in striatum and prefrontal cortex (PFC). The monoamines and their metabolites were assayed by reverse-phase high-performance liquid chromatography with electrochemical detection. Animal SE in striatum presented a decrease in DA and NE levels and an increase in HVA although in PFC there was an increase in DA, 5-HT and NE. Animals that died from cocaine-induced seizures in striatum showed an increase only in NE levels, but on the other hand in PFC a decrease occurred in DA and NE levels. Taken together these results indicated that cocaine-induced SE and death altered monoamine levels in different ways depending on the brain area studied, suggesting that different mechanisms are involved.

This work studied the effects of ethanol in the absence and presence of haloperidol under two experimental conditions. In protocol 1, rats were treated daily with ethanol (4 g/kg, p.o.) for 7 days, and received only haloperidol (1 mg/kg, i.p.) from the 8th day to the 14th day. In protocol 2, animals received ethanol, and the treatment continued with ethanol and haloperidol from the 8th day to the 14th day. Results show increases in alanine transaminase (ALT; 48% and 55%) and aspartate transaminase (AST; 32% and 22%) levels after ethanol or haloperidol (14 days) treatments, as compared with controls. Apolipoprotein A-1 (APO A1) levels were increased by haloperidol, after 7- (148%) but not after 14-day treatments, as compared with controls. Levels of lipoprotein (high-density lipoprotein (HDL-C)) tended to be increased only by ethanol treatment for 14 days. ALT (80%) and AST (43%) levels were increased in the haloperidol plus ethanol group (protocol 2), as compared with controls. However, an increase in APO A1 levels was observed in the haloperidol group pretreated with ethanol (protocol 1), as compared with controls and ethanol 7-day treatments. Triglyceride (TG) levels were increased in the combination of ethanol and haloperidol in protocol 1 (234%) and 2 (106%), as compared with controls. Except for a small decrease in haloperidol groups, with or without ethanol, as related to ethanol alone, no other effect was observed in HDL-C levels. In conclusion, we showed that haloperidol might be effective in moderating lipid alterations caused by chronic alcohol intake.Key words: ethanol, haloperidol, hepatic enzymes, lipid profiles.

1. The study of changes that persist after drug discontinuation could be fundamental to understand the mechanisms involved in craving and relapse. 2. In this work the changes occurring in muscarinic, D1- and D2-like receptors after 30 min (immediate), 1 day (early), 5 and 30 days (late) withdrawal periods were studied, in the striatum of rats treated once a day for 7 days with cocaine 20 and 30 mg/kg, i.p. 3. Binding assays were performed in 10% homogenates and ligands used were [3H]-N-methylscopolamine, [3H]-SCH 23390, and [3H]-spiroperidol for muscarinic (M1 + M2-like), D1-, and D2-like receptors, respectively. 4. Muscarinic receptors presented a downregulation at all doses and discontinuation times, while the dissociation constant (Kd) for this receptor decreased after 30 min, 5 and 30 days abstinence times. In relation to D1-like receptors we found an antagonistic effect with 100% increase in receptor number 30 min after the last cocaine injection, but after 1-day withdrawal a downregulation was observed with both doses that persisted up to 30 days, only with the higher dose. The dissociation constant value (Kd) for this receptor showed a decrease only with 5 and 30 days withdrawal. An increase occurred with D2-like receptors at all doses and withdrawal periods studied, while Kd increased in 30-min, 5, and 30 days withdrawal. 5. In this work we found that the subchronic cocaine treatment produces early and long-lasting modifications in cholinergic muscarinic as well in dopaminergic receptors that persist up to 30 days of cocaine withdrawal.

Hoodia gordonii is a plant species used traditionally in southern Africa to suppress appetite. Recently, it has been associated with a significant increase in blood pressure and pulse rate in women, suggesting sympathomimetic activity. The present study investigated the possible antidepressant-like effects of acute and repeated (15 days) administration of H. gordonii extract (25 and 50 mg/kg, po) to mice exposed to a forced swimming test (FST). Neurochemical analysis of brain monoamines was also carried out to determine the involvement of the monoaminergic system on these effects. Acute administration of H. gordonii decreased the immobility of mice in the FST without accompanying changes in general activity in the open-field test during acute treatment, suggesting an antidepressant-like effect. The anti-immobility effect of H. gordonii was prevented by pretreatment of mice with PCPA [an inhibitor of serotonin (5-HT) synthesis], NAN-190 (a 5-HT1A antagonist), ritanserin (a 5-HT2A/2C antagonist), ondansetron (a 5-HT3A antagonist), prazosin (an α1-adrenoceptor antagonist), SCH23390 (a D1 receptor antagonist), yohimbine (an α2-adrenoceptor antagonist), and sulpiride (a D2 receptor antagonist). A significant increase in 5-HT levels in the striatum was detected after acute administration, while 5-HT, norepinephrine and dopamine were significantly elevated after chronic treatment. Results indicated that H. gordonii possesses antidepressant-like activity in the FST by altering the dopaminergic, serotonergic, and noradrenergic systems.

The present work studied neurochemical changes in rat premotor cortex 30 min, 1 and 5 days after withdrawal from cocaine repeated administration (20 and 30 mg/kg, intraperitoneally, daily for 7 days). Binding assays were performed in 10% homogenates, and ligands used were [(3)H]-N-methylscopolamine, [(3)H]-SCH 23390, and [(3)H]-spiroperidol for muscarinic, D(1)- and D(2)-like receptors, respectively. Levels of cyclic AMP (cAMP) and cyclic guanosine monophosphate (cGMP) were determined using a commercial kit. Scatchard analyses of muscarinic receptors showed an upregulation after 1 and 5 days withdrawal. While D(2)-like receptors were upregulated at all withdrawal periods, D(1)-like receptors were upregulated only at the 30 min withdrawal, and returned to normal levels after 1 day of the last injection. In relation to cAMP levels, the repeated cocaine administration, 1 day after the last injection produced a decrease (around 26%) with both doses, while a 67% increase was seen in cGMP levels with the 30 mg/kg dose. These findings indicate lasting neurochemical changes in premotor cortex caused by cocaine which remained after different withdrawal periods.

The present results show an increase in locomotor activity 24 h following repeated cocaine administration only with the higher dose (10 mg/kg, i.p., daily for 1 week) compared to controls (administered with saline). Binding assays were done and the ligands used were [3H]N-methylscopolamine ([3H]-NMS), [3H]-SCH 23390, and [3H]-spiroperidol to determine muscarinic (M1- and M2-like), D1 and D2 receptors, respectively. Scatchard analyses revealed alterations in Bmax not only for muscarinic, but also for D2-like receptors that were significantly increased. On the other hand, no alterations were detected on D1-like receptors densities and dissociation constant values. However, the Kd value was significantly increased for D2 receptors. The changes in muscarinic receptors were observed predominantly on M2-like, which presented an increase of 84% with the 10 mg/kg, i.p., dose only. On D2-like receptors, increases of 63 and 54% were demonstrated with the doses of 5 and 10 mg/kg, i.p.. The preferential effects of cocaine on muscarinic and D2-like receptors were also demonstrated in vitro where decreases in [3H]-NMS and [3H]-spiroperidol binding were observed. The results indicate that the effects of cocaine on muscarinic and dopaminergic postsynaptic receptors are functions of dose, duration of treatment, and time of drug withdrawal.

Prenatal immune challenge (PIC) in pregnant rodents produces offspring with abnormalities in behavior, histology, and gene expression that are reminiscent of schizophrenia and autism. Based on this, the goal of this article was to review the main contributions of PIC models, especially the one using the viral-mimetic particle polyriboinosinic-polyribocytidylic acid (poly-I:C), to the understanding of the etiology, biological basis and treatment of schizophrenia. This systematic review consisted of a search of available web databases (PubMed, SciELO, LILACS, PsycINFO, and ISI Web of Knowledge) for original studies published in the last 10 years (May 2001 to October 2011) concerning animal models of PIC, focusing on those using poly-I:C. The results showed that the PIC model with poly-I:C is able to mimic the prodrome and both the positive and negative/cognitive dimensions of schizophrenia, depending on the specific gestation time window of the immune challenge. The model resembles the neurobiology and etiology of schizophrenia and has good predictive value. In conclusion, this model is a robust tool for the identification of novel molecular targets during prenatal life, adolescence and adulthood that might contribute to the development of preventive and/or treatment strategies (targeting specific symptoms, i.e., positive or negative/cognitive) for this devastating mental disorder, also presenting biosafety as compared to viral infection models. One limitation of this model is the incapacity to model the full spectrum of immune responses normally induced by viral exposure.

Justicia pectoralis (Acanthaceae) is used as an antiinflammatory, antimicrobial and bronchodilator, and its extract exerts an anxiolytic-like effect profile in animal models. This work presents the behavioral effects of an aqueous standardized extract of Justicia pectoralis (SEJP) in animal models, such as the elevated plus maze (EPM), light/dark, open field, rota rod and pentobarbital sleep time. The extract was administered intragastrically to male mice at single doses of 50, 100 and 200 mg/kg, while diazepam 1 or 2 mg/kg was used as a standard drug and flumazenil 2.5 mg/kg was used to evaluate the participation of benzodiazepinic receptors. The results showed that, similar to diazepam (1 mg/kg), SEJP significantly modified all the observed parameters in the EPM test, without altering the general motor activity in the open field, rota rod and pentobarbital sleep time tests. Flumazenil reversed not only the diazepam effect but also the SEJP effect. In the same way, all doses of SEJP increased the time of permanence in the light box in the light/dark test. The results showed that SEJP presented an anxiolytic-like effect, disproving sedative effects.

In the present study were studied the antinociceptives properties of monoterpene R-(+)-limonene (LM) in chemical and thermal models of nociception in mice. The R-(+)-limonene was administered, intraperitoneally (i.p.), at doses of 25 and 50 mg/kg. The results showed significant inhibition produced on chemical nociception induced by intraperitoneal acetic-acid and in the second phase of subplantar formalin test, but did not manifest a significant effect in hot-plate test. The R-(+)-limonene-induced antinociception in second phase of formalin test was insensitive to naloxone (1 mg/kg, s.c.). It was also demonstrated that R-(+)-limonene (25, 50 mg/kg) neither significantly enhanced the pentobarbital-sleeping time nor impaired the motor performance in rota-rod test, indicating that the observed antinociception is unlikely to be due to sedation or motor abnormality. In conclusion it may be suggested that the R-(+)-limonene presented antinociceptive activity and that, probably, this action can be related with peripheral analgesia, but, not with the stimulation of opioids receptors.

This work was designed to study the influence of drugs during seizures and status epilepticus (SE) induced by pilocarpine and mortality in adult rats. Morphine (0.1 and 0.2 mg/kg), SCH 23390 (0.1 and 0.2 mg/kg), haloperidol (5 and 10mg/kg) and lithium (30 and 60 mg/kg) were administered intraperitoneally (i.p.), 30 min before to pilocarpine (400 mg/kg, s.c.). The animals were observed (24 h) to determine: number of peripheral cholinergic signs, tremors, stereotyped movements, seizures, SE, latency to first seizure and number of deaths after pilocarpine treatment. Morphine and haloperidol had proconvulsant effects in both doses tested. Smaller and higher doses of these drugs no protected and increased pilocarpine-induced seizures, SE and/or mortality. SCH 23390 protected against seizures, increased the latency to first seizure and reduced the mortality of the animals treated with pilocarpine Theses results suggest that dopamine receptor system receptor subtypes exert opposite functions on the regulation of convulsive activity. The morphine is proconvulsant in lower doses. The opioids in high doses tested exert an action proconvulsant during the establishment of epileptic activity induce by pilocarpine. The lithium no protected the animals against seizures induced by pilocarpine and is used which a model of epilepsy associated with lower doses of pilocarpine in several studies, suggesting absence of the effect anticonvulsants in rodents.

This work was designed to study the influence of drugs during seizures and status epilepticus (SE) induced by pilocarpine and mortality in adult rats. Fluoxetine (10 and 20 mg/kg), NMDA ( N -metyl- d -aspartate, 10 and 20 mg/kg), amitriptyline (25 and 50 mg/kg), ketamine (0.5 and 1.0 mg/kg), gabapentin (100 and 150 mg/kg) and pimozide (10 and 20 mg/kg) were administered intraperitoneally, 30 min prior to pilocarpine (400 mg/kg, s.c.). The animals were observed (24 h) to determine: number of peripheral cholinergic signs, tremors, stereotyped movements, seizures, SE, latency to first seizure and number of deaths after pilocarpine treatment. Fluoxetine, amitriptyline, NMDA, and pimozide had proconvulsant effects in both doses tested. Smaller and higher doses of these drugs no protected and increased pilocarpine-induced seizures and/or mortality. Gabapentin and ketamine protected against seizures and reduced the latency to first seizure. Thus, these results suggest that caution should be taken in the selection of pharmacotherapy and dosages for patients with epilepsy because of the possibility of potentiating convulsive process toxicity.

MELO, C. T. V. de. et al. Anxiolytic-Like effects of (O-Methyl)-N-2,6-dihydroxybenzoyl-tyramine (Riparin III) from Aniba riparia (NEES) MEZ (Lauraceae) in mice. Biological & Pharmaceutical Bulletin, Tokyo, v. 29, n.3, p. 451-454, mar. 2006. This work presents behavioral effects of (O-methyl)-N-2,6-dihydroxybenzoyl-tyramine (riparin III) isolated from the unripe fruit of Aniba riparia (NEES) MEZ (Lauraceae) in animal models of open field, rota rod, elevated plus maze and hole board tests in mice. Riparin III (ripIII) was administered orally, in male mice, at single doses of 25 and 50 mg/kg. The results showed that ripIII, at both doses, had no effects on the spontaneous motor activity in the rota rod test nor in the number of squares crossed in the open field test. However, riparin III decreased the number of grooming and rearing. In the plus maze test, ripIII, at both doses increased the following parameters: percentage of entries in the open arms (PEOA), time of permanence in the open arms (TPOA) and percentage of time of permanence in the open arms (PTOA) and at the dose of 50 mg/kg, increased the number of entries in the open arms (NEOA). Similarly, ripIII, at both doses, showed an increase in the number of head dips into the holes of the hole board test. These results show that riparin III presents anxiolytic effects in the plus maze and hole board tests which are not influenced by the locomotor activity in the open field test.

Experimental manipulations suggest that in vivo administration of cholinergic agonists or inhibitors of acetylcholinesterase (AChE) increases the concentration of acetylcholine. Biochemical studies have proposed a role for AChE in brain mechanisms responsible by development to status epilepticus (SE) induced by pilocarpine. The present study was aimed at investigating the changes in AChE activities in hippocampus, striatum and frontal cortex of adult rats after pilocarpine-induced SE. The control group was treated with 0.9% saline (s.c., control group) and another group received pilocarpine (400 mg/kg, s.c.). Both groups were sacrificed 1 h after treatment. The results have shown that pilocarpine administration and resulting SE produced a significant decrease in the AChE activity in the hippocampus (63%), striatum (35%) and frontal cortex (27%) of adult rats. Our results demonstrated a direct evidence of a decrease in the activity of the AChE in rat brain regions during seizure activity that could be responsible by regulation of acetylcholine levels during the establishment of SE induced by pilocarpine.

The EO of Ocimum micranthum was studied for a possible analgesic effect on the acetic acid induced writhing and formalin test in mice and antioedema activities on the carrageenan and dextran induced paw oedema in rats. The EO demonstrated antinociceptive effects, and pretreatment with naloxone did not reverse the antinociception, indicating that the opioid system is not involved. On the other hand, pretreatment with L-arginine (L-arg) reversed the antinociception, suggesting involvement of the nitric oxide (NO) system. The EO did not present an antioedematogenic effect in the carrageenan and dextran models.

Behavioural changes, muscarinic and dopaminergic receptors density and levels of monoamines were measured in striatum of rats after pilocarpine-induced status epilepticus (SE). Wistar rats at the age of 21 days were treated with pilocarpine (400 mg/kg; subcutaneously) whilst the control group was treated with 0.9% saline (s.c.). Both groups were sacrificed 1 h following the treatment. SE induced a muscarinic receptor downregulation of 64% in pilocarpine group. This effect was also observed to be 57% in D 1 and 32% in D 2 . In the dissociation constant ( K d ) values in muscarinic and D 1 receptor no alterations were verified. On the other hand, the K d value for D 2 was observed to increase 41%. High performance liquid chromatography determinations showed 63, 35, 77 and 64% decreases in dopamine, 3-methoxy-phenylacetic acid, serotonin and 5-hydroxyindoleacetic acid contents, respectively. The homovanilic acid level was verified to increase 119%. The noradrenaline content was unaltered. A direct evidence of monoamine levels alterations can be verified during seizure activity and receptor density changes appear to occur in an accentuated way in immature brain during the estabilishment of SE induced by pilocarpine.

Levetiracetam (LEV) is a new antiepileptic drug effective as adjunctive therapy for partial seizures. It displays a unique pharmacological profile against experimental models of seizures, including pilocarpine-induced seizures in rodents. Aiming to clarify if anticonvulsant activity of LEV occurs due to cholinergic alterations, adult male mice received LEV injections before cholinergic agonists' administration. Pretreatment with LEV (30-200 mg/kg, i.p.) increased the latencies of seizures, but decreased status epilepticus and death on the seizure model induced by pilocarpine, 400 mg/kg, s.c. (P400). LEV (LEV200, 200 mg/kg, i.p.) pretreatment also reduced the intensity of tremors induced by oxotremorine (0.5 mg/kg, i.p). [3H]-N-methylscopolamine-binding assays in mice hippocampus showed that LEV200 pretreatment reverts the downregulation on muscarinic acetylcholine receptors (mAChR), induced by P400 administration, bringing back these density values to control ones (0.9% NaCl, i.p.). However, subtype-specific-binding assays revealed that P400- and LEV-alone treatments result in M1 and M2 subtypes decrease, respectively. The agonist-like behavior of LEV on the inhibitory M2 mAChR subtype, observed in this work, could contribute to explain the reduction on oxotremorine-induced tremors and the delay on pilocarpine-induced seizures, by an increase in the attenuation of neuronal activity mediated by the M1 receptors.

The antidiabetic activity of aqueous, ethanolic and hexanic extracts of Bauhinia forficata was investigated in a model of alloxan-induced diabetes in rats. The biochemical parameters studied were: plasma glucose, serum triglycerides, cholesterol, high density lipoprotein (HDL), and low density lipoprotein (LDL). Extracts were administered daily for 7 d at doses of 200 and 400 mg/kg, p.o., 48 h after alloxan injection (60 mg/kg, i.v.). The alloxan-diabetic rats showed significant reductions in plasma glucose, triglycerides, total cholesterol and HDL-cholesterol after treatment with the extracts and glibenclamide (used as standard) as compared to the diabetic controls. Levels of LDL were not altered. In conclusion, our results showed that the plant extracts when administered by gavage may reduce glucose, triglycerides, total cholesterol and HDL-cholesterol levels. These results suggest the validity of the clinical use of B. forficata in the treatment of diabetes mellitus type II.

This work presents behavioral effects of methyl ethers of N-(2,6-dihydroxybenzoyl) tyramine (riparin III) isolated from the unripe fruit of Aniba riparia on the open field, elevated plus maze (EPM), rotarod, hole board, barbiturate-induced sleeping time, tail suspension and forced swimming tests in mice. Riparin III was administered intraperitoneally to male mice at single doses of 25 and 50 mg/kg. The results showed that riparin III with both doses had no effects on spontaneous motor activity in mice or in the rotarod test, but decreased the number of grooming and rearing. At the dose of 50 mg/kg, riparin III increased the number of entries in the open arms of the EPM test as compared with control. Similarly, in the hole-board test, both doses increased the number of head dips. There was a reduction on the sleeping latency with both doses and a prolongation of the pentobarbital-induced sleeping time with the dose of 25 mg/kg. In the tail suspension test, similar to imipramine (30 mg/kg), riparin III at the dose of 50 mg/kg presented a reduction in the immobility time. In the forced swimming test, both doses of riparin III decreased the immobility time. These results showed that riparin III potentiated the barbiturate-induced sleeping time and presented antidepressant- and anxiolytic-like effects.

We studied the effects of ethanol on the levels of norepinephrine, dopamine, serotonin (5-HT) and their metabolites as well as on D1- and D2-like receptors in the rat striatum. Ethanol (2 or 4 g/kg, po) was administered daily by gavage to male Wistar rats and on the 7th day, 30 min or 48 h after drug administration, the striatum was dissected for biochemical assays. Monoamine and metabolite concentrations were measured by HPLC and D1- and D2-like receptor densities were determined by binding assays. Scatchard analyses showed decreases of 30 and 43%, respectively, in D1- and D2-like receptor densities and no change in dissociation constants (Kd) 48 h after the withdrawal of the dose of 4 g/kg. Ethanol, 2 g/kg, was effective only on the density of D2-like receptors but not on Kd of either receptor. Thirty minutes after the last ethanol injection (4 g/kg), decreases of D2 receptor density (45%) as well as of Kd values (34%) were detected. However, there was no significant effect on D1-like receptor density and a 46% decrease was observed in Kd. An increase in dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC), a decrease in norepinephrine, and no alteration in 5-HT levels were demonstrated after 48-h withdrawal of 4 g/kg ethanol. Similar effects were observed in dopamine and DOPAC levels 30 min after drug administration. No alteration in norepinephrine concentration and a decrease in 5-HT levels were seen 30 min after ethanol (4 g/kg) administration. Our findings indicate the involvement of the monoaminergic system in the responses to ethanol.

The present work showed that the intrastriatal injection of 6-OHDA significantly decreases DA, DOPAC and HVA levels in that rat brain structure. Although there is also a decrease in 5-HT levels no changes were observed in 5-HIAA levels as compared to controls. On the other hand, melatonin (2, 5, 10 and 25 mg/kg, i.p., daily for 7 days) treatment starting 1 h after 6-OHDA lesions, partially reverses the decreases caused by 6-OHDA lesions on these neurotransmitter levels, and contents were brought to approximately 50% of that observed in the contralateral sides of controls or of melatonin treated group. Melatonin was more efficient at the doses of 5 and 10 mg/kg, i.p., and effects were similar between the lowest and highest doses characteristic of a bell-shaped type of response. The apomorphine-induced rotational behavior (3 mg/kg, i.p.) was blocked by 60, 89, 78 and 47% after the doses of 2, 5, 10 and 25 mg/kg, i.p., respectively. Similarly, in this case the doses of 5 and 10 mg/kg were also more efficient. Melatonin (5mg/kg) produced an upregulation of D1 receptors associated with a decrease in Kd value. While no change was observed in maximum density of D2 receptors, the Kd value was also decreased.