Low energy reserves are associated with fasting susceptibility in Neotropical nectar bats Glossophaga soricina / Baixas reservas energéticas corporais estão associadas à susceptibilidade ao jejum da espécie Glossophaga soricina

Abstract Neotropical nectar-feeding bats consume large amounts of sugar and use most of their energy-rich diet directly from the bloodstream, suggesting an adaptation towards lower body energy reserves. Here we tested the hypothesis that bats Glossophaga soricina spare the energy costs of storing energy reserves, even if this would represent a risky susceptibility during fasting. Blood glucose concentrations in 18 h fasted bats showed a 40% decrease. Breast muscle and adipose tissue lipids, as well as carcass fatty acids and liver glycogen, were also decreased following fasting. The inability to keep normoglycemia following a short-term fasting (i.e. 28 h) confirm that nectar bats invest little on storing energy reserves and show a severe fasting susceptibility associated to this pattern. Our study also support the general hypothesis that evolutionary specializations towards nectar diets involve adaptations to allow a decreased body mass, which reduces the energy costs of flight while increases foraging time.

Resumo Morcegos nectarívoros que ocorrem na região Neotropical consomem grandes quantidades de carboidratos, e usam a energia obtida da dieta diretamente, a partir da glicose na circulação sanguínea. Esta adaptação sugere que morcegos nectarívoros tenham evoluído no sentido de apresentar adaptações fisiológicas que permitam o baixo armazenamento de reservas energéticas corporais. Nós testamos a hipótese de que morcegos Glossophaga soricina poupam o gasto energético envolvido com a formação de reservas energéticas teciduais, mesmo que isso represente uma arriscada suscetibilidade da espécie frente ao jejum. As concentrações de glicose apresentaram uma diminuição de 40% após 18 h de jejum. As concentrações de lipídios do músculo peitoral e do tecido adiposo, bem como as de ácidos graxos da carcaça e glicogênio hepático também diminuíram após 18 h de jejum. A incapacidade de manter a normoglicemia observada após o jejum de curto-prazo confirma que morcegos nectarívoros desta espécie não investem na formação de reservas energéticas, e apresentam, consequentemente, uma severa susceptibilidade ao jejum. Este estudo suporta a hipótese de que adaptações evolucionárias da espécie envolvem diminuição da massa corporal, reduzindo o custo energético do voo e aumentado o tempo de forrageamento.

Low energy reserves are associated with fasting susceptibility in Neotropical nectar bats Glossophaga soricina.

Neotropical nectar-feeding bats consume large amounts of sugar and use most of their energy-rich diet directly from the bloodstream, suggesting an adaptation towards lower body energy reserves. Here we tested the hypothesis that bats Glossophaga soricina spare the energy costs of storing energy reserves, even if this would represent a risky susceptibility during fasting. Blood glucose concentrations in 18 h fasted bats showed a 40% decrease. Breast muscle and adipose tissue lipids, as well as carcass fatty acids and liver glycogen, were also decreased following fasting. The inability to keep normoglycemia following a short-term fasting (i.e. 28 h) confirm that nectar bats invest little on storing energy reserves and show a severe fasting susceptibility associated to this pattern. Our study also support the general hypothesis that evolutionary specializations towards nectar diets involve adaptations to allow a decreased body mass, which reduces the energy costs of flight while increases foraging time.

Valores hematológicos de bugios pretos (Alouatta caraya) de vida livre da região do Alto Rio Paraná, sul do Brasil / Hematologic values of free-ranging black-and-gold howlers monkeys (Alouatta caraya) from the region of Upper Paraná River, Southern Brazil

Descreveram-se os valores hematológicos de bugios pretos (Alouatta caraya) e estabeleceram-se diferenças entre sexo e idade, de 36 animais aparentemente saudáveis, de vida livre da região do Alto Rio Paraná, sul do Brasil. Os animais foram capturados e contidos quimicamente com cloridrato de tiletamina e cloridrato de zolazepam, na dose média de 5,5mg/kg, por via intramuscular. Na comparação entre os sexos, houve diferença para número de hemácias (4,48±1,36 e 3,58±0,91 x10(6)/mm³), maior nas fêmeas, e volume globular médio (90,99±27,65 e 118,36±44,63fL) e número de eosinófilos (0,30±0,24 e 0,76±0,85 x10³/mm³), maior nos machos. O volume globular (39,46±3,53 e 36,69±3,54 por cento) e a proteína total plasmática (7,91±0,53 e 7,40±0,63g/dL) foram significativamente mais baixos nos animais jovens.

The hematologic values and the influence of gender and age were described in 36 free-ranging healthy black-and-gold howler monkeys (Alouatta caraya) from the region of Paraná river, Southern Brazil. The animals were caught with trap models and intramuscularly anesthetized with 5.5mg/kg tilitamine/zolazepam hydrochlorides. The red blood cells were higher in females (4.48±1,36 vs. 3.58±0.91x10(6)/mm³) while mean corpuscular volume (90.99±27.65 and 118.36±44.63 fL) and eosinophils (0.30±0.24 and 0.76±0.85x10³/mm³) were significant higher in males. The packed cell volume (39.46±3.53 and 36.69±3.54 percent) and plasma total protein (7.91±0.53 and 7.40±0.63g/dL) were lower in juveniles.

Effects of levetiracetam in lipid peroxidation level, nitrite-nitrate formation and antioxidant enzymatic activity in mice brain after pilocarpine-induced seizures.

: Oxidative stress has been implicated in a large number of human degenerative diseases, including epilepsy. Levetiracetam (LEV) is a new antiepileptic agent with broad-spectrum effects on seizures and animal models of epilepsy. Recently, it was demonstrated that the mechanism of LEV differs from that of conventional antiepileptic drugs. Objectifying to investigate if LEV mechanism of action involves antioxidant properties, lipid peroxidation levels, nitrite-nitrate formation, catalase activity, and glutathione (GSH) content were measured in adult mice brain. The neurochemical analyses were carried out in hippocampus of animals pretreated with LEV (200 mg/kg, i.p.) 60 min before pilocarpine-induced seizures (400 mg/kg, s.c.). The administration of alone pilocarpine, 400 mg/kg, s.c. (P400) produced a significant increase of lipid peroxidation level in hippocampus. LEV pretreatment was able to counteract this increase, preserving the lipid peroxidation level in normal value. P400 administration also produced increase in the nitrite-nitrate formation and catalase activity in hippocampus, beyond a decrease in GSH levels. LEV administration before P400 prevented the P400-induced alteration in nitrite-nitrate levels and preserved normal values of catalase activity in hippocampus. Moreover, LEV administration prevented the P400-induced loss of GSH in this cerebral area. The present data suggest that the protective effects of LEV against pilocarpine-induced seizures can be mediated, at least in part, by reduction of lipid peroxidation and hippocampal oxidative stress.

Evaluation of levetiracetam effects on pilocarpine-induced seizures: cholinergic muscarinic system involvement.

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.

Effects of chronic ethanol treatment on monoamine levels in rat hippocampus and striatum

We studied the effects of ethanol on concentrations of noradrenaline (NE), dopamine (DA) and serotonin (5-HT) and their metabolites in rat hippocampus and striatum. Ethanol (2 or 4 g/kg, po, from a 20 percent aqueous solution) was administered daily to male Wistar rats (4-13 per group) for 30 days and animals were sacrificed 30 min or 48 h after the last administration. Monoamines were measured by HPLC and considered significant at P < 0.05. A 47 percent increase in 5-HT levels was observed in the hippocampus with 4 g/kg ethanol in the 30-min protocol. Ethanol (2 and 4 g/kg) decreased DA (2114.5 ± 126.4 and 1785.1 ± 234.2 ng/g wet tissue, respectively) and 3,4-dihydroxyphenylacetic acid (DOPAC, 1477.6 ± 132.1 and 1218.8 ± 271.7 ng/g wet tissue, respectively) levels, while the higher dose also decreased NE (159.8 ± 13.5), 5-HT (228.0 ± 46.8) and 5-hydroxy-3-indoleacetic acid (5-HIAA, 304.4 ± 37.2 ng/g wet tissue), in the striatum after a 48-h withdrawal as compared to controls (DA: 3063.9 ± 321.3; DOPAC: 2379.6 ± 256.0; NE: 292.8 ± 50.2; 5-HT: 412.4 ± 36.2; 5-HIAA: 703.9 ± 61.4 ng/g wet tissue). In the 30-min protocol, ethanol (2 or 4 g/kg) decreased striatal NE (66 and 70 percent) and DA (50 and 36 percent) levels. On the other hand, increases were seen in 5-HIAA (146 and 153 percent) and 5-HT (59 and 86 percent) levels. Ethanol (2 g/kg, po) increased the homovanillic acid (HVA)/DA ratio (129 percent) in the striatum in the 30-min protocol, while at the higher dose it increased the HVA/DA ratio in the 48-h protocol (61 percent). These results indicate alterations in monoamines, mainly in the striatum, after chronic ethanol, which are influenced by dose and by the length of time after the last drug administration.

Effects of chronic ethanol treatment on monoamine levels in rat hippocampus and striatum.

We studied the effects of ethanol on concentrations of noradrenaline (NE), dopamine (DA) and serotonin (5-HT) and their metabolites in rat hippocampus and striatum. Ethanol (2 or 4 g/kg, po, from a 20% aqueous solution) was administered daily to male Wistar rats (4-13 per group) for 30 days and animals were sacrificed 30 min or 48 h after the last administration. Monoamines were measured by HPLC and considered significant at P < 0.05. A 47% increase in 5-HT levels was observed in the hippocampus with 4 g/kg ethanol in the 30-min protocol. Ethanol (2 and 4 g/kg) decreased DA (2114.5 +/- 126.4 and 1785.1 +/- 234.2 ng/g wet tissue, respectively) and 3,4-dihydroxyphenylacetic acid (DOPAC, 1477.6 +/- 132.1 and 1218.8 +/- 271.7 ng/g wet tissue, respectively) levels, while the higher dose also decreased NE (159.8 +/- 13.5), 5-HT (228.0 +/- 46.8) and 5-hydroxy-3-indoleacetic acid (5-HIAA, 304.4 +/- 37.2 ng/g wet tissue), in the striatum after a 48-h withdrawal as compared to controls (DA: 3063.9 +/- 321.3; DOPAC: 2379.6 +/- 256.0; NE: 292.8 +/- 50.2; 5-HT: 412.4 +/- 36.2; 5-HIAA: 703.9 +/- 61.4 ng/g wet tissue). In the 30-min protocol, ethanol (2 or 4 g/kg) decreased striatal NE (66 and 70%) and DA (50 and 36%) levels. On the other hand, increases were seen in 5-HIAA (146 and 153%) and 5-HT (59 and 86%) levels. Ethanol (2 g/kg, po) increased the homovanillic acid (HVA)/DA ratio (129%) in the striatum in the 30-min protocol, while at the higher dose it increased the HVA/DA ratio in the 48-h protocol (61%). These results indicate alterations in monoamines, mainly in the striatum, after chronic ethanol, which are influenced by dose and by the length of time after the last drug administration.

Effects of ethanol and haloperidol on plasma levels of hepatic enzymes, lipid profile, and apolipoprotein in rats.

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.

Cocaine treatment causes early and long-lasting changes in muscarinic and dopaminergic receptors.

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.

Melatonin reverses neurochemical alterations induced by 6-OHDA in rat striatum.

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 (5 mg/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.

Inhibitory action of a calcium channel blocker (nimodipine) on seizures and brain damage induced by pilocarpine and lithium-pilocarpine in rats.

The present work studied the effect of a calcium channel blocker (nimodipine) on rat behavioural changes and brain lesions observed after seizures induced by high doses of pilocarpine (400 mg/kg, s.c.; P400), and the association of lithium (3 mEq/kg, i.p., daily during 7 days) plus pilocarpine (a single dose of 15 mg/kg, s.c.) administered 24 h after the last injection of lithium. In the P400 model, nimodipine (5 or 10 mg/kg, i.p.) inhibited convulsions, status epilepticus, and significantly decreased the percentage of death and cerebral changes (Mann-Whitney, P = 0.0057). In the lithium-pilocarpine (Li-Pi) induced seizures, nimodipine even increased convulsive action and did not interfere with brain lesions. The results suggested that a calcium channel mechanism is involved in the P400 induced seizures, and that there is a difference in the physiopathology of epileptic seizures and brain damage induced by either P400 and Li-Pi models.