The effect of nootropics on impared learning performance in a pole jumping test after repeated ethanol administration

The influence of ethanol administration (4 ml of 10% ethanol/d p.o.) for 6 and 13 d respectively, on learning behaviour of rats has been studied using an active avoidance reaction. While the formation of an active avoidance reaction was only insignificantly impaired by the application of ethanol for 6 d, the learning performance of rats showed a significant deficit after 13d of ethanol ingestion. Repeated nootropic pretreatment (d11 to 14 following first ethanol dose b.i.d.) resulted in an attenuation of learning deficits. The nootropics piracetam (100 mg/kg i.p.) methyl-glucamine orotate (225 mg/kg i.p.), meclofenoxate hydrochloride (100 mg/kg i.p.), pyritinol (100 mg/kg i.p.) and dihydroergotoxine mesilate (1 mg/kg i.p.) showed to be effective. The possible mechanism of action is discussed.     

The effects of lindane, DDT, and chlordecone on avoidance responding and seizure activity

Male adult Fischer-344 rats were given various doses of lindane (0, 15, and 30 mg/kg, po), chlordecone (0, 25, 50, or 100 mg/kg, ip), or p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT) (0, 25, 50, or 100 mg/kg, po) and tested for their ability to perform a two-way shuttle box task or to learn and retain a step-through passive avoidance response. Administration of p,p'-DDT or chlordecone 3 hr prior to acquisition did not affect the number of shuttle box avoidance responses made during a 60-trial training task, while responses during the intertrial interval (ITI) were decreased. Rats receiving 15 or 30 mg/kg of lindane made fewer avoidance responses, but did not differ from controls in terms of the number of responses during the ITI. When 30 mg/kg lindane was given 3 hr prior to passive avoidance acquisition, retention was impaired 7 days later; the lower dose of lindane, and all doses of chlordecone or p,p'-DDT had no effect under these conditions. When these chemicals were given immediately after passive avoidance training, animals treated with lindane were not affected. Animals receiving 100 mg/kg of p,p'-DDT or chlordecone displayed marked signs of toxicity and animals tested 7 days after training showed an impaired retention. Pretreatment with anticonvulsants such as phenobarbital and chlordiazepoxide, which may enhance GABA-mediated responses, blocked the disruptive effects of lindane (30 mg/kg) on shuttle box avoidance. The seizure-related activity produced by a higher dose of lindane (60 mg/kg) and kainic acid, a hippocampal excitotoxin, was also blocked by phenobarbital and chlordiazepoxide. Pretreatment with phenytoin, which is thought to bind to the inactivation gates of sodium, had no effect on the effects produced by lindane or kainic acid. These data suggest that treatment with nonconvulsant doses of lindane can interfere with the ability to acquire and use new information and that these effects may be associated with alterations in GABA.     

Vinpocetine: nootropic effects on scopolamine-induced and hypoxia-induced retrieval deficits of a step-through passive avoidance response in rats

Vinpocetine, vincamine, aniracetam, and Hydergine, compounds with purported cognition activating activity, were evaluated for their ability to prevent scopolamine-induced and hypoxia-induced impairment of passive avoidance retention (24 hr) in rats. Vinpocetine (peak effect dose [PED]= 200 mg/kg PO), aniracetam (PED = 100 mg/kg PO), vincamine (PED = 30 mg/kg PO), and Hydergine (PED = 1 mg/kg PO) prevented memory disruption by scopolamine. Vinpocetine (PED = 3 mg/kg PO) and aniracetam (PED = 30 mg/kg PO) were also effective in preventing disruption of passive avoidance retention impaired by 7% oxygen hypoxia. In contrast, Hydergine (0.05 to 3 mg/kg PO) and vincamine (0.3 to 100 mg/kg PO) were not effective against hypoxia-induced impairment. Hydergine at doses greater than 10 mg/kg PO markedly impaired motor function. In both tests the protection was dose-related for all test substances in an inverted U-shaped manner. Mecamylamine (1, 3, 10 mg/kg SC), (-)-nicotine (0.1 to 0.4 mg/kg SC), apovincaminic acid (1-400 mg/kg PO) and pemoline (1-100 mg/kg PO) did not protect against memory impairment induced by either procedure. These data support the view that vinpocetine, a compound chemically distinct from the pyrrolidinones, has a cognitive activating ability as defined in models of both scopolamine-induced and hypoxia-induced memory impairment in rats.     

Physostigmine induced hippocampal theta activity and learning in rats

Summary The effect of physostigmine on EEG activity and conditioning was studied in rats. Theta activity develops in the hippocampus of curarized or freely moving unanesthetized animals 3–7 min after i.p. injection of 1 mg/kg physostigmine salicylate, attains maximum after 10 min and disappears after 30–60 min. Gradual impairment of learning corresponds to the development of theta waves. One-trial acquisition of a passive avoidance reaction (avoiding a compartment with electrifiable floor) is completely suppressed 10 min after application of 1.0 or 0.5 mg/kg physostigmine and to a lesser extent even after 0.2 mg/kg physostigmine. No retention of this reaction was found 24 h after onetrial learning when physostigmine (0.5 mg/kg) was applied 8 min before the retention test. On the contrary the same physostigmine dose does not impair the retention of an overtrained (four times) passive avoidance reaction. Also retention of an overlearned active avoidance reaction (running to the safe part of the apparatus is not affected by 0.5 mg/kg physostigmine and only partly impaired by 1 mg/kg physostigmine. The functional significance of the hippocampal theta activity is discussed.     

A comparative study of the nootropic properties of piracetam and oxiracetam]

The behavioral activities of piracetam and oxiracetam were studied during the learning tests (active avoidance, passive avoidance, T-maize). The levels of the orientation reaction and emotionality of the animals were determined by the "open field" method. To achieve similar effects, injections of 10 mg/kg of oxiracetam and 100 mg/kg of piracetam intraperitoneally were required. Both nootropics facilitated the learning of the animals but failed to change their behavior in the open field. Piracetam was more effective in the active avoidance test and oxiracetam in the T-maize test. The data indicate some differences in the activities of piracetam and oxiracetam.     

Effects of 2-Ethylhexanoic Acid on Reproduction and Postnatal Development in Wistar Rats

Reproductive toxicity of 2-ethylhexanoic acid (2-EHA) was studiedin Wistar rats. The animals (24 animals per sex per group) weregiven 2-EHA as a sodium salt in drinking water at daily dosesof 100, 300, or 600 mg/kg. Control animals received plain water.Male rats were exposed to 2-EHA for 10 weeks and females for2 weeks prior to mating, both sexes during the mating periodand females during the entire gestation and lactation period.2-EHA caused a slight but dose-dependent decrease in fertility;time to mating increased at 300 and 600 mg/kg and even totalinfertility ensued. 2-EHA slightly decreased sperm quality inmales. The spermatozoa were significantly less motile at 100and 600 mg/kg and abnormal sperm occurred more frequently atthe two highest dose levels. The average litter size was reducedby 16% in the dose group receiving 600 mg/kg. The birth weightsof the pups were unaffected but the body weight gain was transientlyslower during lactation at 600 mg/kg. Several pups appearedabnormal (kinky tail, lethargic, slightly paralyzed legs) andthe physical development assessed by several landmarks (openingof eyes, eruption of teeth, hair growth) and reflexes (gripreflex, cliff avoidance) was delayed at 300 and 600 mg/kg. Inanother experiment, a single dose of 600 mg/kg 2-EHA was givento pregnant females by gavage on Gestational Day 4, 5, 6, or7 and the number of implantations were counted on GestationalDay 10. Administration on Day 6 decreased the number of implantationsand caused resorptions. In conclusion, 2-ethylhexanoic acidcaused impaired fertility in Wistar rats and delayed postnataldevelopment of pups. The reduced fertility might result fromdisturbed implantation in uterus and the retarded developmentof pups from teratogenicity and pre- and postnatal toxic effectsof 2-EHA.     

Combined action of uranium and stress in the rat. I. Behavioral effects

The influence of restraint stress on uranium (U)-induced behavioral effects was assessed in adult male rats. Eight groups of animals received uranyl acetate dihydrate (UAD) in the drinking water at doses of 0, 10, 20 and 40 mg/kg/day during 3 months. Rats in four groups were concurrently subjected to restraint during 2 h per day throughout the study. At the end of the period of uranium exposure, the following behavioral tests were carried out: open-field activity, passive avoidance and Morris water maze. Uranium concentrations in brain were also determined. At 10 and 20 mg/kg/day of UAD restraint significantly affected the total distance traveled in the open-field during the first and third periods tested, respectively, while no significant differences between groups were observed on the passive avoidance test. In the Morris water maze test, the influence of restraint was only significant on the latency time measured on Day 3 in rats exposed at 10 mg/kg/day. Restraint stress did not affect significantly the uranium levels in brain of rats. Although the results of the present study scarcely show uranium-induced behavioral effects at the oral doses of UAD here administered, these effects, as well as the slight influence of restraint stress noted in some tests should not be underrated.     

Improvement of shuttle-box avoidance by combinations of orotic acid and central stimulants

The effect of orotic acid and central stimulants on retention of shuttle-box avoidance was investigated in rats. Orotic acid (100 mg/kg) was injected 30 min before training; caffeine (20 mg/kg), strychnine (1 mg/kg), or methylphenidate (10 mg/kg) were injected immediately after training. When given alone, these drugs improved avoidance retention when tested 24h after training. However, improvement of retention was much more evident when orotic acid was given in combination with a stimulant. The data are discussed in relation to the role of macromolecule synthesis and arousal in memory formation.     

JTT-608 controls blood glucose by enhancement of glucose-stimulated insulin secretion in normal and diabetes mellitus rats

We investigated the pharmacological effects of a new anti-hyperglycemic agent, JTT-608 [trans-4-(4-methylcyclohexyl)-4-oxobutyric acid], in normal and neonatally streptozotocin-treated rats. In normal rats, JTT-608 improved glucose tolerance at 3-30 mg/kg, doses that did not cause a decrease in fasting blood glucose levels. In contrast, tolbutamide (10-100 mg/kg) and glibenclamide (1-3 mg/kg) caused a persistent decrease in fasting blood glucose levels, and tolbutamide only improved glucose tolerance at 10-100 mg/kg. Furthermore, JTT-608 (3-30 mg/kg) enhanced insulin secretion only with glucose stimulation, but tolbutamide (10-100 mg/kg) enhanced it both with and without glucose stimulation. In neonatally streptozotocin-treated rats, JTT-608 (10-100 mg/kg) improved glucose tolerance with enhanced insulin secretion in the oral glucose tolerance test and meal tolerance test. Additionally, JTT-608 improved glucose tolerance dose dependently, but the effect of tolbutamide reached a plateau. We conclude that JTT-608 is an enhancer of glucose-stimulated insulin secretion.     

Characteristics of learning and memory impairment induced by delta9-tetrahydrocannabinol in rats

We investigated the characteristics of delta9-tetrahydrocannabinol (THC)-induced impairment of learning and memory using an 8-arm radial maze task, a water maze, a visual discrimination task with 2 figures and a passive avoidance test in rats. THC (6 mg/kg, i.p.) impaired spatial memory in the standard task of the 8-arm radial maze. THC (4-6 mg/kg, i.p.) selectively impaired working memory in a reference and working memory task of the 8-arm radial maze. Even at a dose of 10 mg/kg, THC did not impair spatial memory in the water maze. In addition, THC at a dose of 6 mg/kg, which had inhibitory effects in the 8-arm radial maze, did not affect performance in the visual discrimination task. These results indicate that at low doses (2-6 mg/kg), THC may not produce visual function abnormalities. THC impaired retrieval (6 mg/kg, i.p.) as well as acquisition (10 mg/kg, i.p.) in the passive avoidance test. The consolidation process was also impaired by i.c.v. injection (100 microg), but not i.p. injection (6-10 mg/kg) of THC. These results suggest that THC-induced impairment of spatial memory is based on the selective impairment of working memory through its effects on acquisition and retrieval processes.     

Further studies on BL-3912A: effects on avoidance behavior of rats with low baselines and on reaction thresholds to electric footshock.

Rats selected for their low performance baselines in an active avoidance shuttle box task were given various doses of R-(-)-2-amino-1-(2,5-dimethoxy-4-methylphenyl) butane (BL-3912A), S-amphetamine or piracetam. BL-3912A at 1 mg/kg IP had no significant behavioral effects, while 5 and 10 mg/kg significantly increased the number of avoidance responses without affecting responses during the intertrial interval (ITI). Statistically reliable effects on behavior were not observed following 20 mg/kg of BL-3912A. S-Amphetamine at 0.5 and 1 mg/kg IP also facilitated avoidance responding, but could be differentiated from BL-3912A in that the S-amphetamine significantly increased shuttles during the ITI. S-Amphetamine at 0.1 mg/kg was not effective, while 2 mg/kg increased ITI activity. Piracetam (50 or 200 mg/kg) had no significant effects on avoidance or shuttles during ITI. Using an electric shock titration procedure, BL-3912A at 10 and 20 mg/kg IP had no significant effect on reaction thresholds. Animals receiving 100 mg/kg of p-chlorophenylalanine po for 3 days and tested 2 days later showed hyperalgesia to the electric shock. In summary, BL-3912A facilitated shuttle box avoidance responding of rats with low performance baselines. Behavioral facilitation occurred without concomitant increases in noncontingent activity or apparent changes in reactivity to electric footshock.     

Influence of nootropic drugs on the learning- and memory-impairing effect of diethyldithiocarbamate in albino rats

The effects of four nootropic drugs (piracetam, aniracetam, meclofenoxate and fipexide) on the impaired cognitive functions by the dopamine-beta-hydroxylase inhibitor diethyldithiocarbamate (DDC) were investigated in albino rats. The changes in learning and memory were studied by the two-way active avoidance with punishment reinforcement (shuttle box). DDC injected intraperitoneally at a dose of 300 mg/kg in the course of the 5-day shuttle box training significantly impaired learning and retention. The 10-day treatment (5 days before and 5 days during training) with piracetam 600 mg/kg, aniracetam 50 mg/kg, meclofenoxate 100 mg/kg and fipexide 10 mg/kg completely abolished the learning- and memory-impairing effect of DDC. The role of the NA-ergic neurotransmitter system for the DDC-induced disturbances in cognition as well as for the protective effects of nootropic drugs was discussed.     

Effect of phenyl-tert-butylnitrone, mexidol and nooglutil on the ischemic lesion zone and memory in rats following middle cerebral artery occlusion

An ischemic cerebral affection zone amounting to 22.51 +/- 3.0% of the ipsilateral hemisphere volume was found on the frontal brain sections in the frontoparietal cortex of rats 72 h after occlusion of the distal branch of the medial cerebral artery. The new nootropic drug nooglutyl [N-(5-hydroxynicotinoyl)-L-glutamic acid] in a dose of 10 mg/kg, as well as mexidol or phenyl-tert-butylnitrone (PBN) in a dose of 100 mg/kg, introduced into the vein at the moment of occlusion and intraperitoneally for two days after operation, effectively restricted the affected zone: nooglutyl, up to 7.6 +/- 2.28%; mexidol, up to 9.55 +/- 1.9%; and PBN, up to 12.8 +/- 1.7% of the ipsilateral hemisphere volume. On the third day after operation, animals preliminarily learnt to the passive avoidance conditioned reflex exhibited violated memory retrieval. The retrieval was significantly improved in the test animals treated with mexidol and especially nooglutyl.     

Concurrent exposure to aluminum and stress during pregnancy in rats: Effects on postnatal development and behavior of the offspring

The present study was conducted to assess the potential combined influence of maternal restraint stress and aluminum (Al) exposure on postnatal development and behavior in the offspring of exposed rats. Female rats were concurrently exposed to 0 (control group), 50 or 100 mg/kg/day of Al administered as Al nitrate nonahydrate in drinking water with citric acid (355 or 710 mg/kg/day) for a period of 15 days prior to mating with untreated males. Aluminum exposure was maintained throughout the gestational, lactational and post-weaning periods. On days 6-20 of gestation, one-half of the pregnant animals in each group were restrained for 2 h/day. Food consumption and maternal body weight were decreased in the groups exposed to restraint only or combined with the highest Al dose. All of the animals were allowed to deliver and wean their offspring. The pups were evaluated for physical development and neuromotor maturation. Moreover, open-field activity, passive avoidance, and spatial learning in a water maze were also determined on postnatal days 30, 35 and 60, respectively. Body weight of pups treated with 100 mg/kg/day of Al was decreased relative to controls from postnatal day 12 through 21, sexual maturation was delayed in Al treated females and in males exposed to 100 mg/kg/day. Forelimb grip strength was reduced in males exposed to 100 mg/Al/kg/day and in females exposed to this Al dose plus prenatal restraint. Learning in a passive avoidance task indicated facilitated performance for Al treated rats at 100 mg/kg/day combined with prenatal restraint as evidenced by longer avoidance latencies, while learning in a water maze task showed a shorter latency to find the platform on acquisition day 2 for Al treated rats. However, no effects of Al on water maze performance were detected during the retention probe trial in which the only effect noted was an increase in the platform quadrant swim time for the prenatal restraint group. In general terms, the results of the present study did not show a notable influence of maternal restraint on the Al-induced postnatal developmental and behavioral effects in the offspring of prenatally Al-exposed rats.     

Effect of semicarbazide on the perinatal development of the rat: changes in DNA, RNA and protein content

Semicarbazide was injected intraperitoneally to pregnant rats in single doses of 50, 75, 100 or 150 mg/kg. Treatment was administered on days 7, 10 or 13 of pregnancy. Semicarbazide produced abnormalities in 21 day old fetuses, found mainly in liver and kidney and in the skull and sternum, as well as resorptions and fetal deaths throughout gestation. This substance also caused a high postnatal mortality rate during the first month of life, especially with the 100 mg/kg dose. This dose reduced the nucleic acid and protein content in the lung and liver of the rats whether they were adult, pregnant, fetus or newborn. Statistically significant decrease of the nucleic acid level in adult rats appeared 48 hours after treatment. This decrease varied in the two organs studied. The lungs of pregnant rats which received semi-carbazide on day 10 of gestation showed a statistically significant decrease of the nucleic acid and protein levels on day 18 of gestation; there was also a significant decrease of RNA in the liver on this day, while a decrease in the proteins did not appear until day 21. The fetuses of treated mothers showed a significant decrease of DNA and RNA in the lung when they were 21 days old and a continuous decrease of the protein levels lasting up to the end of the first week of life. DNA and RNA in the liver of these offspring decreased when they were 30 days old. As for the protein content, it decreased throughout fetal life and continued to do so during the first month of fetal life.     

Effects of selective inhibition of N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) on mice in learning and memory tasks

The purpose of the present study was to examine the effects of 2-(phosphonomethyl)-pentanedioic acid (2-PMPA), a selective inhibitor of N-acetylated-alpha-linked-acidic dipeptidase (NAALADase, glutamate carboxypeptidase II), an enzyme catalyzing the cleavage of glutamate from the neuropeptide N-acetyl-aspartyl-glutamate (NAAG), on memory processes in mice. Long-term memory was evaluated in step-through passive avoidance task while alternation behavior, as a measure involving spatial working memory, was assessed in Y-maze task. Additionally, horizontal activity was evaluated by means of electronically monitored locomotor activity system. The mice were treated with either 2-PMPA (50, 100 and 150 mg/kg i.p.) or N-methyl-d-aspartate (NMDA) receptor antagonist, (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10-imine hydrogen maleate (MK-801) at doses of: 0.05, 0.1, 0.15 and 0.2 mg/kg i.p., as a comparator. In the passive avoidance task, the drugs were administered once before or immediately after training, and before retention test. 2-PMPA at the doses used did not affect retention of passive avoidance; however, it increased the latency to enter the dark box during the training day. In the Y-maze task, 2-PMPA (150 mg/kg i.p.) impaired spontaneous alternation and reduced locomotion while the lower dose of 100 mg/kg was ineffective. In the locomotor activity test, 2-PMPA (100 and 150 mg/kg i.p.) did not significantly affect horizontal activity. MK-801 (0.2 mg/kg i.p.) injected before training reduced retention in the passive avoidance task. In the Y-maze task, MK-801 (0.1 mg/kg i.p.) impaired alternation behavior and considerably increased locomotion in the Y-maze and locomotor activity test. These results indicate that NAALADase inhibition may impair alternation behavior.     

Immunotoxicity of tributyltin oxide in rats exposed as adults or pre-weanlings

A comparison was made between adult and pre-weanling rats of the immunotoxic effects of subacute dosing with bis(tri-n-butyltin) oxide (TBTO). Adult (9 weeks old) male Fischer rats were dosed by oral gavage with TBTO for 10 consecutive days at 1.25-10 mg/kg per dose or 3 times/week for a total of 10 doses at 5-20 mg/kg per dose. Adult rats similarly dosed by oral gavage with 6 mg/kg per dose cyclophosphamide (CY) served as positive controls. Pre-weanling rats (3-24 days old) were dosed 3 times/week for a total of 10 doses at 2.5, 5 or 10 mg/kg per dose. At various times after dosing rats were evaluated for alterations in body and lymphoid organ weights, mitogen and mixed lymphocyte reaction (MLR) lymphoproliferative (LP) responses, natural killer (NK) cell activity, cytotoxic T lymphocyte (CTL) responses and primary antibody plaque-forming cell (PFC) responses. In adult rats given 10 daily doses of TBTO, thymic involution was observed at a dosage of 2.5 mg/kg and mitogen responses to Con A and PHA were suppressed at 5 mg/kg. The PFC response was enhanced in adult rats dosed daily at 2.5 mg/kg. A dosage of 5 mg/kg given intermittently (3 times/week) to adults or pre-weanlings resulted in thymic involution. Reductions in mitogen responses were observed in adults dosed intermittently at 10 and 20 mg/kg and in pre-weanlings at 5 and 10 mg/kg. The MLR response was suppressed in adult rats dosed intermittently at 20 mg/kg and in pre-weanling rats at 10 mg/kg. NK cell activity was suppressed only in pups dosed intermittently at 10 mg/kg. CTL responses were not affected in either age group. Within 3 weeks following the last exposure of adult rats to TBTO all parameters returned to normal. On the other hand, LP responses to mitogens were suppressed in 10-week-old rats that were dosed with 10 mg/kg TBTO as pre-weanlings. However, this exposure regimen in reductions in body weight that persisted for up to 13 weeks of age, which suggests that TBTO may be a developmental toxicant. These data indicate that while exposure of young rats to TBTO resulted in immune alterations at doses lower than those required to suppress responses in adults, the observed effects may also be influenced by the developmental toxicity of this compound.     

Influence of NMDA, a potent agonist of glutamate receptors, on behavioral activity in 4-week streptozotocin-induced diabetic rats

The study was designed to investigate the effects of NMDA receptor agonist on the behavioral activity in rats with experimental diabetes mellitus (DM). Experimental diabetes was induced by a single intravenous injection of streptozotocin at a dose of 65 mg/kg dissolved in saline. Rats treated with saline (0.9%) served as control. Stimulation of the NMDA glutamatergic receptor was evoked by ip injection of an agonist N-methyl-D-aspartate acid (NMDA), at a dose of 15 mg/kg 30 min before the experiments. Memory motivated affectively was evaluated in the passive avoidance responses. Possible influence of the treatment on locomotor and exploratory activity was tested in open field test. Moreover, the working memory was evaluated in the T-maze test. We observed that NMDA given alone did not have significant influence on motor activity in control rats except for the number of bar approaches, while in rats with DM NMDA significantly increased motor activity in the open field test. In rats with experimental diabetes, NMDA increased acquisition, but it did not have any significant influence on consolidation and recall of a passive avoidance responses. NMDA at the tested dose had no influence on a passive avoidance latency in control rats. In the T-maze test, NMDA increased working memory but only in diabetic rats.     

Effect of an NMDA receptor agonist on T-maze and passive avoidance test in 12-week streptozotocin-induced diabetic rats

This study examined behavioral effects mediated by NMDA (N-methyl-D-aspartic acid) receptors in 12-week streptozotocin (STZ)-induced diabetic rats. Effects of an NMDA receptor agonist on behavior in the open field test, passive avoidance test and T-maze were examined in control groups of rats and in rats with diabetes mellitus (DM). We have used 116 rats for experiments. Experimental type I diabetes was induced by a single intravenous injection of streptozotocin at a dose of 65 mg/kg, dissolved in citrate buffer. Stimulation with the NMDA receptor agonist at a dose of 15 mg/kg was performed 30 min before the experiments. In control rats, NMDA increased the number of crossing and rearings in the open field test, improved acquisition and consolidation processes and did not influence recall in the passive avoidance situation and was ineffective in the T-maze. Diabetes significantly inhibited locomotor and exploratory activity and profoundly impaired acquisition, consolidation and recalling in a passive avoidance, and significantly decreased working memory in T-maze. NMDA treatment of diabetic rats significantly improved memory in passive avoidance and T-maze. The NMDA receptor agonist increased locomotor activity in open field test. The obtained results suggested that stimulation of NMDA receptors had beneficial effects on learning and memory in type I diabetic rats.     

Low dose 4-MBC effect on neuroendocrine regulation of reproductive axis in adult male rats

4-Methylbenzylidene camphor (4-MBC) is an ultraviolet absorbent. The objective of this paper was to evaluate the effect of 4-MBC low-dose exposure on the neuroendocrine reproductive regulation in male rats. Wistar male adult rats were injected sc. with 4-MBC during 5 days with a dose of 2 and 10mg/kg or during 2 days with a dose of 2 and 20mg/kg. In all rats serum prolactin, LH and FSH concentration were assayed. The hypothalamus of rats injected during 2 days were also dissected to study GnRH release. Rats that received 2 and 10mg/kg of 4-MBC during 5 days showed a decrease in the LH and FSH serum concentration. In rats injected during 2 days, serum LH decreased with 2 and 20mg/kg and FSH decreased with 2mg/kg of 4-MBC. In vitro hypothalamic GnRH release also decreased in these animals. These results show that low doses of 4-MBC inhibit the reproductive axis in adult male rats.