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PubMed1990

Maternal age does not affect tetrahydrocannabinol's in utero actions in rats.

The potential contribution of maternal age to tetrahydrocannabinol's (THC) in utero effects in rats was studied. Pregnant animals were intubated with 25, 10 or 0 mg/kg of THC from gestation day six to parturition. Animals in the 10 and 0 mg/kg groups were pair fed to those given the 25 mg/kg dose. Each series of doses was administered to females three, four or six months of age. THC lowered maternal weight gain and weights of offspring at birth and at 21 days of age, but did not affect litter size, spontaneous alternation or passive avoidance learning in offspring. Increased maternal age was associated with smaller litter size and lower birth weight and weight at 21 days, but did not interact significantly with THC.

Animals↗

PubMed1984

Dual action of cycloheximide on memory formation in day-old chicks.

Amnesia for a single trial discriminated passive avoidance learning task in day-old chicks, resulting from the antibiotic cycloheximide, is shown to begin after 30 min following learning when cycloheximide is given immediately after or before learning. However, amnesia does not begin until after 50 min following learning when cycloheximide is given 5 min or later after learning. The results are interpreted in the context of a 3 stage model of memory formation. It is suggested that the second or intermediate stage involves two phases: phase A which lasts up to 30 min following learning, is energy dependent, and is susceptible to inhibition by 2,4-dinitrophenol; phase B which occurs after phase A, lasts up to 50 min following learning, is energy independent, and is not susceptible to inhibition by 2,4-dinitrophenol. It is concluded that cycloheximide given immediately after or before learning inhibits expression of phase B of intermediate memory as well as formation of long-term memory, while cycloheximide given 5 min or later after learning only inhibits formation of long-term memory. Another antibiotic, anisomycin, is shown to have no effect on intermediate memory, independent of time of administration.

2,4-Dinitrophenol↗

PubMed1986

Exploratory behavior, learning ability, and thyroid hormonal responses to stress in female rats rehabilitating from postnatal hypothyroidism.

Newborn female Long-Evans rats were divided into groups of normal, hypothyroid [0.1% propylthiouracil (PTU) a reversible antithyroid goitrogen in the litter's drinking water], and hypothyroid rehabilitated (PTU water from birth to day 25, normal water thereafter). The rats were tested for several adaptive behavioral tasks between 40 and 90 days of age. At day 50, serum concentration of TSH and thyroid hormones revealed no detectable amounts of T4 and a 10-fold increase in TSH in the hypothyroid rats. At the same age in the rehabilitated animals, TSH levels were still below normal, a deficit fully normalized by day 90. Normal 50-day-old rats responded to pain stress (electric footshocks) by a significant depression of serum T4 and elevation of T3 levels within 10 min of treatment, whereas the rehabilitated animals exhibited an opposite pattern of response, i.e., an increase in the circulating T4 and a decrease in T3. At 50 days of age, both hypothyroid and rehabilitated rats showed decreased exploratory activity and no habituation in the hole-board test, whereas the locomotor activity of the rehabilitated females was significantly higher than that of the normals. No differences were found in the scores of passive avoidance learning (one trial step-through) among the three groups. Similarly, the rate of acquisition of the active one-way conditioned avoidance response (CAR) of the hypothyroid and rehabilitated rats did not differ significantly from that of the controls. However, the hypothyroid rats required significantly more unconditioned stimuli (footshocks) to acquire CAR and showed longer response latency and less intertrial responses. Although the hypothyroid rats showed no extinction of CAR, the rehabilitated rats were capable of extinction to an extent indistinguishable from normal rats. But compared with the normal animals, the rehabilitated rats showed significantly higher intertrial activity during both the acquisition and extinction phases of CAR.

Animals↗

PubMed1999

Essential role for TrkB receptors in hippocampus-mediated learning.

Brain-derived neurotrophic factor (BDNF) and its receptor TrkB regulate both short-term synaptic functions and long-term potentiation (LTP) of brain synapses, raising the possibility that BDNF/TrkB may be involved in cognitive functions. We have generated conditionally gene targeted mice in which the knockout of the trkB gene is restricted to the forebrain and occurs only during postnatal development. Adult mutant mice show increasingly impaired learning behavior or inappropriate coping responses when facing complex and/or stressful learning paradigms but succeed in simple passive avoidance learning. Homozygous mutants show impaired LTP at CA1 hippocampal synapses. Interestingly, heterozygotes show a partial but substantial reduction of LTP but appear behaviorally normal. Thus, CA1 LTP may need to be reduced below a certain threshold before behavioral defects become apparent.

Animals↗

PubMed1999

Behavioral effects of aluminum in mice: influence of restraint stress.

The influence of restraint stress on potential aluminum (Al)-induced behavioral changes was assessed in CD-1 mice. Three groups of adult mice were given 0, 300 and 600 mg Al/kg body weight per day in drinking water for 2 weeks. One-half of the animals in each group were concurrently subjected to restraint stress during 1 h per day throughout the study. After cessation of treatment, open-field activity, active avoidance learning, and motor resistance and coordination of the animals were evaluated. At the end of the behavioral testing period, mice were killed and Al concentrations were determined in a number of tissues. There were no remarkable effects of Al, restraint stress or their combined administration on either open-field activity or on the number of avoidances in an automatic reflex conditioner. However, a lower motor resistance and coordination in a rotarod were observed following exposure to Al at 600 mg/kg/day, restraint alone or concurrent administration of Al (300 and 600 mg/kg/day) plus restraint stress. The levels of Al in whole brain and cerebellum were significantly enhanced in mice exposed to Al plus restraint. Although the present results scarcely show Al-induced neurobehavioral effects, the influence of restraint stress on Al levels in whole brain and cerebellum can be the basis for further studies on the potential role of this element in certain neurological disorders.

Aluminum↗

PubMed1996

Enhanced hippocampal corticotropin-releasing factor gene expression associated with memory consolidation and memory storage in rats.

Corticotropin-releasing factor (CRF) has been found to play an important role in modulating the learning and memory processes in rats. In the present study, we examined the alteration of CRF mRNA level in rat hippocampus at different stages of the memory process. Results indicated that CRF mRNA is quite homogenously distributed within subdivisions of the hippocampus, with the dentate gyrus (DG) has a relatively lower expression level. By using the one-way inhibitory avoidance learning paradigm, we have selected the good memory (GM) rats (with a retention score of 600) and the poor memory (PM) rats (with retention scores < 80). Results indicated that CRF mRNA level in the hippocampus was significantly increased in GM rats when compared with that in the PM rats at 1 hr, 3 hr and 6 hr after training. It was not markedly altered at 24 hr and 72 hr post-training. However, it was again increased at 21 days post-training in both the hippocampus and the frontal cortex. Further, this effect was demonstrated not to be associated with the acute footshock stress. These results together suggest that enhanced hippocampal CRF gene expression is probably associated with both memory consolidation and memory storage, but is not associated with maintenance of formed memory in rats.

Animals↗

PubMed1981

Interaction of genotype and fostering in the development of behavior of DBA and C57 mice.

Effects of fostering on behavior were studied in DBA/1Bg and C57BL/10Bg mice. Two-day-old pups were either infostered to mothers of their own strain, crossfostered to mothers of the other strain, or left as controls with their own mothers. Body weight, latency of emergence into an open field, open-field activity, defecation in an open field, spontaneous alternation, passive avoidance learning, and active escape learning were measured when the mice were 22 and 43 days old. Strain differences were observed for each trait except for spontaneous alternation. Fostering per se affected open-field activity and active escape learning. Similar effects of fostering per se on aggressive behavior have been reported by others. These may involve a role of ovarian cytoplasm, X-chromosomal genes, or uterine environment.

Animal Husbandry↗

PubMed1984

Effect of nucleus accumbens destruction in rat.

The paper presents the effects of nucleus accumbens destruction in rats. There are certain behavioral correlates (e.g., avoidance learning and dominance) which are influenced by the destruction of the nucleus accumbens, while other specific correlates are not significantly affected (namely, open field movements and competition for food). The results are discussed.

Animals↗

PubMed1990

[Behavioral teratogenesis and placental, milk, and blood-brain barrier transfer following prenatal and postnatal exposures to chlorpromazine in rats].

In order to determine behavioral teratogenesis of fetal and neonatal exposures to chlorpromazine (CPZ) in rats, conditioned avoidance learning by shuttle box in pups was examined. CPZ was administered sc to pregnant and nursing rats during fetal organogenesis period (on days 11-15 of gestation, at doses of 9, 21 mg/kg/day), perinatal period (on days 16-20 of gestation, at 9, 18 mg/kg/day), and nursing period (on days 1-10 postpartum, at 9, 18 mg/kg/day). The results showed that high doses of CPZ during all periods caused learning impairment in pups, although learning impairment by the exposures during fetal organogenesis and nursing periods was stronger than that of perinatal exposure and pattern of learning impairment was different between the former and the latter. Exposure to CPZ during fetal organogenesis period induced an increase in norepinephrine and dopamine concentrations in the hippocampus of pups. Thus it is clear that developmental treatment with CPZ produced learning impairment. Furthermore, CPZ transferred rapidly into fetal and neonatal brains. Our results suggest that blood-brain barrier transfer of CPZ is a major factor in behavioral teratogenesis.

Animals↗

PubMed1999

Effects of prenatal zidovudine treatment on learning and memory capacities of preweanling and young adult mice.

The present study analyzed the short and long-term effects of prenatal zidovudine (AZT) exposure on learning and memory capacities of CD-1 mice. Two tasks normally used in rodents were used, namely a passive avoidance step-through task and a Morris navigation task. AZT (0, 0.4, and 0.8 mg/ml) was administered via drinking water to pregnant CD-1 females from day 10 of gestation to delivery. Data on reproductive performance, such as gestation length, litter size, and pup mortality were collected. Avoidance learning in the offspring was tested on postnatal day (PND) 15, while spatial learning performances in the Morris water maze were obtained on PND 45. Retention of the passive avoidance response was mildly impaired in the offspring exposed to the 0.8 mg/ml AZT solution, whereas spatial learning on PND 45 was unaffected.

Animals↗

PubMed1991

The effects of atrial natriuretic peptide on electroconvulsive shock-induced amnesia in rats. Transmitter-mediated action.

Electroconvulsive shock (ECS) applied immediately after passive avoidance learning in rats caused partial amnesia. This could be prevented by administering r-ANP into the lateral brain ventricle. The effects of pre-treatment with different receptor blockers: (haloperidol, atropine, phenoxybenzamine, propranolol, naloxone, bicuculline and methysergide) on the ANP-induced antiamnesia were investigated. The receptor blockers per se in the doses selected had no influence on the ECS-induced amnesia. Haloperidol, atropine and propranolol blocked the antiamnestic action of the peptide, while phenoxybenzamine, naloxone, bicuculline and methysergide were ineffective. The results confirm our previous observations that ANP might play a role in learning and memory processes and also suggest that the antiamnestic action of the peptide is mediated by dopaminergic, cholinergic and beta-adrenergic mediator systems.

Amnesia↗

PubMed2006

Impaired bidirectional synaptic plasticity and procedural memory formation in striatum-specific cAMP response element-binding protein-deficient mice.

The striatum has a well documented role in procedural learning and memory. However, the synaptic and molecular mechanisms of acquisition and storage of this form of memory remain poorly understood. We examined procedural memory and plasticity in transgenic mice reversibly expressing a dominant-negative cAMP response element-binding protein (CREB) mutant in the dorsal striatum. In these transgenic mice, corticostriatal long-term potentiation and depression are abolished, indicating that CREB function is essential for bidirectional long-term synaptic plasticity in this structure. Importantly, CREB-deficient animals show reversible alterations in several forms of striatum-dependent memory, including footshock avoidance learning and "response" learning in the cross maze. These findings implicate transcriptional regulation by CREB family transcription factors in striatum-dependent information processing and provide the first clear correlation between procedural learning and memory and synaptic plasticity at the corticostriatal synapse.

Animals↗

PubMed2003

The influence of diazepam on atropine reversal of behavioural impairment in dichlorvos-treated rats.

Acute effects on the behaviour of the organophosphate insecticide dichlorvos and its standard antidotes possessing behavioural activity, atropine and diazepam, were studied separately and in combinations in male Wistar rats. In the spontaneous locomotor activity test, dichlorvos and diazepam decreased, whereas atropine increased performance. The effect of dichlorvos was obtained at a dose (5 mg/kg) that induced overt intoxication, and could not be reversed during first half hour-period after administration of any combination of drugs. In the other two tests, active avoidance learning and rotarod performance, the effective dose of dichlorvos (2 mg/kg) was devoid of somatic signs of intoxication. In these more sensitive tests, the effective atropine dose (40 mg/kg) completely reversed dichlorvos-induced incapacitation. In the rotarod test, diazepam (0.5 mg/kg) contributed to the incapacitating effect of dichlorvos, and impeded desirable influence of atropine as well. In the active avoidance test, diazepam (2.5 mg/kg) contributed to failure to escape; it did not influence the dichlorvos-induced decrease of avoidance performance, nor did it impair the completely reversing effects of atropine. The results point to the possible summation of acute incapacitating effects of organophosphates and diazepam on motor performance, which seems to be, at least partly, antagonized by sufficiently high doses of atropine. However, taking into account the long-term neuroprotective role of the anticonvulsant diazepam, and hence its delayed beneficial influences on behaviour, the immediate testing of atropine/diazepam treatment of organophosphate intoxication in active avoidance paradigm could possess beside sensitivity the predictive value as well.

Animals↗

PubMed2003

Behavioural changes in rats treated with a neurotoxic dose regimen of dextrorotatory amphetamine derivatives.

Repeated administration of amphetamine derivatives is reported to induce neurotoxicity in rat brain. Methamphetamine (MA) impairs the function of both the dopaminergic and serotonergic systems, 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) affects primarily the latter system. The neurochemical deficits induced by these amphetamines have been described in detail, but relatively few data have been reported regarding the behavioural consequences of the neurotoxic treatment. The aim of the present study was to investigate short- and long-term behavioural consequences of treatment with neurotoxic doses of (+)MA or (+)MDMA. Spontaneous locomotor activity in novel surroundings and cognitive function (avoidance behaviour) were evaluated. Rats were treated with four s.c. injections of 10 mg/kg (+)MA or (+)MDMA with a 2-hour interval between each injection. Behavioural tests were then carried out 3 days, 1, 2 and 4 weeks after these treatments. A reduction of spontaneous locomotor activity in novel surroundings was detected 3 days after the treatment with the study drugs, but not after 1, 2 and 4 weeks. No change in passive and active avoidance learning was observed. The lack of marked behavioural changes after a neurotoxic dose regimen indicates that some compensatory mechanisms may develop and counterbalance the neurochemical changes induced by these amphetamine compounds.

Animals↗

PubMed1994

Intrahippocampal administration of both the D- and the L-isomers of AP5 disrupt spontaneous alternation behavior and evoked potentials.

We previously reported that systemically administered N-methyl-D-aspartate (NMDA) antagonists significantly impair spontaneous alternation behavior. Others have reported that the restricted blockade of hippocampal NMDA receptors disrupts performance on different tests of spatial learning and have suggested that the resulting impairments are attributable to a disruption of endogenous NMDA-dependent long-term potentiation (LTP). In the present study, we determined whether spontaneous alternation performance was disrupted by circumscribed blockade of hippocampal NMDA receptors as well as by a second class of compounds which disrupt LTP, protein kinase inhibitors. The effect of hippocampal NMDA blockade on inhibitory avoidance was also examined insofar as this behavior too is disrupted by systemically administered NMDA antagonists. When injected into the hippocampus 15 min prior to spontaneous alternation testing, the NMDA antagonists CPP and D,L-AP5 each decreased alternation rates. The specific protein kinase C (PKC) inhibitor, NPC 15437, also disrupted spontaneous alternation, whereas the more general kinase inhibitor, PMXB, did not. When injected 15 min prior to inhibitory avoidance training, CPP also impaired inhibitory avoidance learning as assessed during a subsequent test session, 48 h later. Interpretation of these data was complicated by the additional findings that intrahippocampal infusion of L-AP5 (which is inactive with respect to NMDA receptors) also disrupted alternation performance, and that both the D- and the L-isomers of AP5 as well as each kinase inhibitor dramatically disrupted evoked responses (i.e., population spike amplitude, spike latency, and EPSP slope), as recorded in the dentate gyrus and evoked by perforant path stimulation. These data indicate that behaviorally effective doses of AP5 may have effects which extend beyond NMDA blockade. Moreover, the effects of these compounds on hippocampal transmission, in general, suggest that attribution of the amnestic consequences of their administration to impaired LTP may be unwarranted.

2-Amino-5-phosphonovalerate↗

PubMed1986

The effect of lesions in the mesencephalic reticular formation upon conditioned avoidance responses in rat. III. Lesions of the area subcuneiformis.

Two groups of 6 month old male hooded rats of the Long-Evans strain with bilateral symmetrical lesions in the anterior part of the mesencephalic area subcuneiformis (CUS) were compared with two sham-operated control groups (each group n = 8). CUS rats were absolutely unable to acquire a conditioned avoidance response (CAR) in a jump test; they even did not find out the escape possibility. Postoperative CAR acquisition of CUS rats in a horizontal alley was not different from controls, but their running speed was decreased (p less than 0.005). Lesioned rat's postoperative acquisition of brightness-discrimination was evidently disturbed and their error rate was still enhanced after 120 trials (p less than 0.005). Their reaction times of leaving the start box, however, were significantly lowered. The postoperative retention of preoperatively learnt CAR was very low. Relearning was possible in the Y-maze at lower level, but impossible in the jump test. The error rate decreased very slowly in the postoperative testing, whereas controls performed the brightness discrimination without errors as before. The unconditioned escape, however, was performed as correctly by CUS rats in the jump test as in the preoperative trials but rather slowly. The pattern of the behavioural syndrome after CUS lesions and the deficits in avoidance learning are possibly caused by a loss in sensory-motor coupling and a weakened ability to select visual, olfactory or painful stimuli which are important for the regulation of certain forms of behaviour.

Animals↗

PubMed1994

Behavioral and immunological events induced by electrical stimulation of the rat midbrain periaqueductal gray region.

We report here on the immunological and behavioral alterations induced by stimulation of the mesencephalic periaqueductal gray matter (PAG), a component of the brain aversive system. Male Wistar rats were implanted with stimulating electrodes in the caudal dorsolateral part of the PAG. After recovery, animals were screened for aversive behavior, characterized by running, jumping, vocalization or freezing reaction. Then, rats were subdivided to those which could control aversive stimulation (AS) by switch-off response (cAS group) and those which could not interrupt AS (uAS group). After sensitization with bovine serum albumin (BSA) in complete Freund's adjuvant, rats were stimulated 3 times/week for 40 days, each session lasting 30 min/rat. Immunological assessment included antibody production and hypersensitivity skin reactions to BSA 14 and 21 days after immunization. A behavioral profile of aversively stimulated animals was determined by a poststartle response, open field (OF) activity and two-way shuttle-box avoidance task. The results revealed elevated antibody production to BSA in cAS and lowered in uAS rats, compared to sham-stimulated and intact controls. Arthus and delayed hypersensitivity skin reactions increased in PAG-stimulated animals on day 14 but not on day 21 after immunization. Poststartle response was enhanced both in cAS and uAS rats. Along with immunopotentiation, administration of cAS produced hyperactivity in OF test and facilitation of the active avoidance learning, whereas uAS caused only moderate suppression of rearing in a novel OF environment. Physiological implications and possible mechanisms that may account for PAG-mediated immunobehavioral changes are outlined.

Animals↗

PubMed1989

Nucleus basalis magnocellularis lesions facilitate two-way active avoidance.

Bilateral ibotenic acid lesions of the nucleus basalis magnocellularis (NBM), which resulted in 30% depletion of cortical choline acetyltransferase, facilitated acquisition of shuttlebox two-way active avoidance learning in rats. These results contrast with a report of impaired two-way active avoidance after bilateral electrolytic lesions of the NBM, but support findings of facilitation after ibotenic acid lesions. The data suggest that electrolytic lesions impair shuttlebox learning by damaging fibers of passage in the vicinity of the NBM.

Acetylcholinesterase↗