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At least 973 records · Page 54Linked to original sources
PubMed1997

Unilateral lesions of the dorsal striatum in rats disrupt responding in egocentric space.

Rats were trained in a specially designed, multichoice operant chamber on a visual choice reaction time task designed to assess performance on each side of the rat's body. The task required animals to sustain a nose poke in a central hole, until a brief light stimulus was presented in either of two holes that were located on the same side of the box. Once the rats were trained to perform the task to both sides independently they received unilateral injections of quinolinic acid into the dorsal striatum. Postoperatively, lesioned animals were impaired when performing the task on the side contralateral to the lesion. The time taken to initiate contralateral responses was increased. Contralateral responses were also exclusively biased toward the nearer of the two response locations, regardless of the location of the stimulus. This was interpreted as a specific impairment in generating responses in contralateral space. In contrast, no comparable deficit was seen when the animals performed the task on the side ipsilateral to the lesion. Additional postoperative challenges, in which response options were presented bilaterally, showed this response deficit to be defined in egocentric coordinates, with the severest response deficits for the most contralateral locations.

Animals↗
PubMed1988

Hippocampal but not astrocyte transplants enhance recovery on a forced choice alternation task after kainate lesions.

In rats, intrahippocampal injections of kainate produced selective lesions of the CA3 pyramidal cells and a performance deficit on a forced-choice alternation task. Transplants of embryonic hippocampus significantly facilitated recovery on the alternation task whereas hippocampal transplants taken from adult donors showed a similar but non-significant trend in recovery. Previous data have shown that after frontal cortex ablation transplants of cultured astrocytes facilitated behavioral recovery. After hippocampal lesions however transplants of cultured astrocytes, either before or after kainate injections, did not facilitate recovery on the alternation task. Trophic activity produced by astrocytes did not appear to be sufficient to enhance the rate of recovery. Replacement of damaged neurons may be required for the observed enhanced behavioral recovery.

Animals↗
PubMed1983

The use of nonverbal pragmatic behaviors by language-impaired and normal-speaking children.

The use of six nonverbal pragmatic behaviors was investigated for three groups of subjects. The experimental group (LI) consisted of 20 language-impaired children who were in stages III and IV of linguistic development. One control group (NSY) consisted of 20 normal-speaking children equated with the experimental group on the basis of mean length of utterance. Another control group (NSO) consisted of 20 normal-speaking children equated with the experimental group by chronologic age. The NSY were younger, whereas the NSO were of the same age as the LI. Two individuals observed each child and a peer playing with toys and recorded the presence of the six behaviors for each subject. The LI and the NSY and the NSO did not differ significantly for five behaviors. Play was the only behavior that distinguished the groups. The clinical implications of the results are discussed.

Child, Preschool↗
PubMed1988

Deficits in spontaneous behavior and cognitive function following systemic administration of kainic acid.

Recurrent seizures leading to status epilepticus were induced in rats by a 10 mg/kg subcutaneous injection of kainic acid (KA). After a 4-day recovery period, the KA-treated animals showed a syndrome of increased activity in an open field, hyperreactivity in response to handling, and deficits in acquisition of both passive avoidance and spatial learning tasks. The second experiment demonstrated that KA also caused deficits in learning to approach a visible platform in a water maze. Two months after the initial treatment, the animals were still hyperactive and deficient in passive avoidance acquisition; however, they performed normally on the spatial learning task. These results reflect both the convulsive effects of KA, which produce transient retardation, and the brain damage to limbic system structures, which accounts for the permanent deficits.

Animals↗
PubMed2005

Learning and memory after neonatal exposure to 3,4-methylenedioxymethamphetamine (ecstasy) in rats: interaction with exposure in adulthood.

This study determined whether developmental and adult 3,4-methylenedioxymethamphetamine (MDMA) exposures in rats have interactive effects on body temperature, learning, other behaviors, and monoamine concentrations in the hippocampus, prefrontal cortex, and striatum. Learning was assessed in the Cincinnati water maze (CWM), Morris water maze (MWM), and novel object recognition (NOR). On acquisition trials in the MWM, significant differences from developmental MDMA exposure were found on latency, cumulative distance, path length, and angle of first bearing to the goal, but the early and adult MDMA exposure group performed no worse than the developmental-only MDMA group. In the reversal trials, however, an interaction was seen: latency to the goal, cumulative distance, and angle of first bearing were increased in animals treated both developmentally and in adulthood with MDMA compared with those treated only developmentally. Other tests (elevated zero maze, CWM, NOR, and open-field activity) did not show an interaction, nor did hippocampal concentrations of serotonin or dopamine. However, several behavioral tests showed neonatal MDMA effects, including increased errors in the CWM, reduced time spent with a new object in the NOR test, and reduced locomotor activity in the open-field. By contrast, adult MDMA decreased the number of entries into open quadrants of the elevated zero maze. Litter effects were controlled by treating litter as the experimental unit and using mixed models repeated measures analyses. Correlational analyses suggested that the MWM reversal interaction involves multiple monoamine changes. The results indicate that developmental MDMA exposure can interact with adult exposure to interfere with some aspects of learning.

Age Factors↗
PubMed1985

Motivational properties of kappa and mu opioid receptor agonists studied with place and taste preference conditioning.

The reinforcing properties of various opioid agonists acting preferentially on the kappa and mu opioid receptors were assessed using taste and place preference conditioning procedures. Kappa receptor agonists produced conditioned aversions. Taste aversions were produced by all of the drugs used, including racemic mixtures of ethylketazocine, tifluadom, and U50-488, and active isomers (+)-tifluadom, (-)-bremazocine, and Mr 2034; corresponding inactive isomers either produced no effect of were less potent. Place aversions were produced by U50-488 and (-)-bremazocine, but not (+)-bremazocine or any of the other kappa receptor agonists tested with the taste procedure. The mu agonists produced predominantly conditioned preferences. Place preferences were produced by morphine, fentanyl and sufentanil. Taste preferences were produced by low doses of these substances; at higher doses the taste preferences were absent or replaced by aversions. Finally, with naloxone and lithium chloride it was shown that the taste procedure was more sensitive to punishing effects than the place procedure. It is concluded that kappa and mu opioid receptor agonists are effective unconditioned stimuli. From the lower portions of the dose response curves it is further concluded that activation of kappa opioid receptors has aversive properties and activation of mu receptors appetitive reinforcing properties. The findings are also discussed with regard to the prevailing notions of taste conditioning with opiates, and the reinforcing properties of activity of the endogenous opioid peptide systems.

Animals↗
PubMed1997

Long-term consequences of neonatal exposure to diazepam on cerebral glucose utilization, learning, memory and anxiety.

The long-term consequences of neonatal exposure to diazepam (DZP) on behavioral abilities and local cerebral glucose utilization (LCGU) in 12 brain regions involved in the control of memory and anxiety were studied in adult rats. Rat pups received a daily subcutaneous injection of 10 mg/kg DZP or of the dissolution vehicle from postnatal day (P) 2 to 21. Learning and memory were tested in P60-P70 rats over 5 consecutive days in a T maze and an eight-arm maze while anxiety and reaction to novelty were tested in a two-compartment box with a two-step staircase on the enriched side. LCGU was measured in the P60 rat by the quantitative autoradiographic [14C]deoxyglucose method. In the T maze, when performed without delay between the two trials, the rate of alternation was significantly lower in DZP- than in vehicle-exposed rats on the first 2 days of testing and similar in both groups on days 3-5. In the procedure with a 30 s intertrial delay, the rate of alternation was similar in DZP- and vehicle-treated rats on all days of testing. In the eight-arm maze, DZP-treated rats were more active, i.e., entered more arms per minute than control animals. The number of arms entered before the first error was lower on day 1 and higher on day 3 in DZP- compared to vehicle-exposed rats. In the two-compartment box, DZP-treated rats crossed more often and spent more time than controls on the lower step of the staircase while control rats made more rearings and spent more time than DZP-exposed rats in the well protected corner of the box. LCGU were decreased by early DZP exposure in six regions which were mammillary body, septum, visual and prefrontal cortices, dorsomedian caudate nucleus and mediodorsal thalamus. In conclusion, postnatal DZP treatment induced at adulthood an increase in activity, a delay in task acquisition but no learning-memory impairment and reduced the level of anxiety allowing active responding to novelty. These quite subtle behavioral changes were accompanied by discrete metabolic decreases in regions mediating anxiety, reflecting a change in the level of anxiety and emotionality.

Animals↗
PubMed2000

Overexpression of alpha2C-adrenoceptors impairs water maze navigation.

We investigated the role of overexpression of alpha2C-adrenoceptors in water maze navigation in mice transgenically manipulated to have a threefold overexpression of the alpha2C-adrenoreceptors. Alpha2C-adrenoreceptors overexpressing mice swam more in the peripheral annulus of the pool and did not find the hidden escape platform as well as the wild type control mice. A subtype-nonselective alpha2-adrenoreceptor antagonist, atipamezole (ATI, 1000 microg/kg, s.c.), fully reversed the deficit in platform finding and search strategy in overexpressing mice. Noradrenaline depletion (-95%) induced by N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) did not impair platform finding of wild type or overexpressing mice. The DSP-4 lesion slightly increased swimming in the peripheral annulus in wild type mice, but not in overexpressing mice. The DSP-4 lesion produced a dissociable effect on the action of atipamezole to improve platform finding and search strategy in overexpressing mice: atipamezole did not alleviate the platform finding deficit in DSP-4 lesioned overexpressing mice, but normalized their abnormal search strategy. These results suggest that the abnormal search pattern and deficit in the accuracy of platform finding are mediated by constitutive activity of overexpressed alpha2C-adrenoreceptors.

Adrenergic alpha-Antagonists↗
PubMed2003

Developing mechanisms of temperamental effortful control.

Studies of temperament from early childhood to adulthood have demonstrated inverse relationships between negative affectivity and effortful control. Effortful control is also positively related to the development of conscience and appears as a protective factor in the development of behavior disorders. In this study, the development of attentional mechanisms underlying effortful control was investigated in 2- to 3-year-old children, as indexed by their performance in a) making anticipatory eye movements to ambiguous locations and b) resolving conflict between location and identity in a spatial conflict task. The ability to make anticipatory eye movements to ambiguous locations within a sequence was clearly present at 24 months. By 30 months, children could also successfully perform a spatial conflict task that introduced conflict between identity and location, and at that age, children's success on ambiguous anticipatory eye movements was related to lower interference from conflict in the spatial conflict task. Children's performance on the eye-movement task was correlated with performance and reaction time on spatial tasks, and both were related to aspects of effortful control and negative affect as measured in children's parent-reported temperament.

Child, Preschool↗
PubMed1993

Hippocampal mediation of stimulus representation: a computational theory.

The authors propose a computational theory of the hippocampal region's function in mediating stimulus representations. The theory assumes that the hippocampal region develops new stimulus representations that enhance the discriminability of differentially predictive cues while compressing the representation of redundant cues. Other brain regions, including cerebral and cerebellar cortices, are presumed to use these hippocampal representations to recode their own stimulus representations. In the absence of an intact hippocampal region, the theory implies that other brain regions will attempt to learn associations using previously established fixed representations. Instantiated as a connectionist network model, the theory provides a simple and unified interpretation of the functional role of the hippocampal region in a wide range of conditioning paradigms, including stimulus discrimination, reversal learning, stimulus generalization, latent inhibition, sensory preconditioning, and contextual sensitivity. The theory makes novel predictions regarding the effects of hippocampal lesions on easy-hard transfer and compound preexposure. Several prior qualitative characterizations of hippocampal function--including stimulus selection, chunking, cue configuration, and contextual coding--are identified as task-specific special cases derivable from this more general theory. The theory suggests that a profitable direction for future empirical and theoretical research will be the study of learning tasks in which both intact and lesioned animals exhibit similar initial learning behaviors but differ on subsequent transfer and generalization tasks.

Animals↗
PubMed2007

Tumor necrosis factor-alpha and its inducer inhibit morphine-induced rewarding effects and sensitization.

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is emerging as an important modulator of the function of the central nervous system (CNS). We have demonstrated that TNF-alpha or Leu-Ile, a TNF-alpha inducer, inhibits methamphetamine-induced rewarding effects and sensitization. In this study, we investigated the effects of TNF-alpha or Leu-Ile on morphine (MOR)-induced rewarding effects and sensitization. METHODS: Levels of TNF-alpha messenger RNA (mRNA) and protein were determined by real-time reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. Effects of TNF-alpha or Leu-Ile on MOR-induced rewarding effects and sensitization were investigated by conditioned place preference and locomotor activity tests. Extracellular dopamine levels were examined using in vivo microdialysis. Effects of TNF-alpha or Leu-Ile on MOR-induced antinociceptive effect and withdrawal symptoms were examined by hot plate test and naloxone-precipitated withdrawal. RESULTS: Morphine induced TNF-alpha mRNA expression via dopamine and opioid receptors. Posttreatment with TNF-alpha or Leu-Ile attenuated the MOR-induced place preference and sensitization even after their development, as well as pretreatment with TNF-alpha or Leu-Ile blocked them. An inhibitory effect of Leu-Ile on MOR-induced place preference was not observed in TNF-alpha knockout mice. Tumor necrosis factor-alpha or Leu-Ile inhibited the increase in extracellular dopamine levels in the nucleus accumbens induced by repeated MOR treatment. CONCLUSIONS: These results suggest that TNF-alpha inhibits MOR-induced rewarding effect and sensitization by regulating extracellular dopamine levels, and Leu-Ile inhibits them via the induction of TNF-alpha.

Animals↗
PubMed2004

The use of acute ethanol administration as a tool to investigate multiple memory systems.

The discovery of multiple memory systems supported by discrete brain regions has been one of the most important advances in behavioral neuroscience. A wealth of studies have investigated the role of the hippocampus and related structures in supporting various types of memory classifications. While the exact classification that best describes hippocampal function is often debated, a specific subset of cognitive function that is focused on the use of spatial information to form hippocampal cognitive maps has received extensive investigation. These studies frequently employ a variety of experimental manipulations including brain lesions, temporary neural blockade due to cooling or discrete injections of specific drugs. While these studies have provided important insights into the function of the hippocampus, they are limited due to the invasive nature of the manipulation. Ethanol is a drug that is easily administered in a non-invasive fashion, is rapidly absorbed and produces effects only in specific brain regions. The hippocampus is one brain region affected by acute ethanol administration. The following review summarizes research from the last 20 years investigating the effects of acute ethanol administration on one specific type of hippocampal cognitive function, namely spatial memory. It is proposed that among its many effects, one specific action of acute ethanol administration is to produce similar cognitive and neurophysiological effects as lesions of the hippocampus. Based on these similarities and the ease of its use, it is concluded that acute ethanol administration is a valuable tool in studying hippocampal function and multiple memory systems.

Animals↗
PubMed2004

Intra-amygdala administration of polyamines modulates fear conditioning in rats.

Amygdalar NMDA receptor activation has been implicated in the acquisition of fear memories in rats. However, little is known about the role of endogenous modulators of the NMDA receptor, such as polyamines, in pavlovian fear-conditioning learning. Therefore, in the present study we investigated whether the immediate pretraining or post-training bilateral infusion of arcaine, an antagonist of the NMDA receptor polyamine-binding site, or spermidine, an agonist of the NMDA receptor polyamine-binding site, into the amygdala affected classical fear conditioning in rats. Bilateral microinjections of arcaine (0.0002-0.2 nmol) decreased, whereas spermidine (0.002-20 nmol) increased, contextual and auditory fear conditioning. Arcaine coadministration, at a dose that had no effect per se, reversed the facilitatory effect of spermidine. These results provide evidence that endogenous and exogenous polyamines modulate the acquisition or early consolidation (or both) of the fear-conditioning task in the amygdala.

Amygdala↗