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At least 433 records · Page 24Linked to original sources
PubMed2006

Reversal of learned helplessness by selective serotonin reuptake inhibitors in rats is not dependent on 5-HT availability.

Serotonin (5-HT) and 5-HT(1A) receptors have been suggested to play a pivotal role in the mechanism of action of antidepressant drugs, particularly in the case of selective serotonin reuptake inhibitors (SSRIs). In the rat learned helplessness (LH) paradigm, a valid animal model of human depression, repeated treatment with the 5-HT(1A) receptor agonist 8-OH-DPAT (0.125 and 0.5mg/kg) and several classes of antidepressants such as the tricyclic agent desipramine (30 and 60mg/kg), the monoamine oxidase inhibitor (MAOI) pargyline (60mg/kg) and the SSRIs fluoxetine (15 and 30mg/kg), paroxetine (15 and 30mg/kg) and sertraline (30mg/kg) improved behavioural deficit in helpless rats. The involvement of serotonergic mechanisms in the antidepressant-like effect of these agents was investigated using the selective 5-HT(1A) receptor antagonist WAY 100,635 and the 5-HT synthesis inhibitor p-chlorophenylalanine (PCPA). Pretreatment with WAY 100,635 blocked the 8-OH-DPAT-induced reduction in escape failures, but did not counteract the antidepressant effect of fluoxetine and paroxetine. PCPA given alone did not modify helpless behaviour nor did it affect the behavioural effect of 8-OH-DPAT, fluoxetine and paroxetine. Adaptive changes in 5-HT(1A) receptor function were studied by measuring 8-OH-DPAT-mediated hypothermia and lower lip retraction (LLR) in the animals 24h after LH test session. Fluoxetine and paroxetine treatments caused a marked reduction in agonist-induced responses, an effect completely prevented by WAY 100,635 and PCPA. In conclusion, whereas direct agonist activity at postsynaptic 5-HT(1A) receptors attenuated helpless behaviour, the antidepressant-like effect of SSRIs was found to be independent of their actions on either 5-HT(1A) receptor function or extracellular 5-HT.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1998

Place learning in hippocampal rats and the path integration hypothesis.

Although two decades of research suggests that the hippocampus plays a special role in place learning, the present paper describes a series of studies using swimming pool spatial tasks that show that hippocampal rats have considerable place learning ability, which includes the abilities of finding, remembering, and searching for places. The same studies also show that when environmental cues are uninformative, as is the case early in original learning and again in reversal learning, hippocampal rats are impaired. Since control rats quickly resolve spatial ambiguity in these situations, it is argued that they must have a system with which they can calibrate spatial cues. The discussion considers the possibility that they use dead reckoning with path integration, a spatial strategy that provides guidance based on cues generated by a point of reference and subsequent self-movement and not the cues in the environment through which they are moving. With path integration an animal can monitor its location and at the same time attach spatial meaning to cues that it encounters. An ability to recalibrate external cues may provide the tuning that allows control rats to quickly acquire place responses while hippocampal rats are constrained by the processes of associative learning.

Animals↗
PubMed1991

Clonidine reverses spatial learning deficits and reinstates theta frequencies in rats with partial fornix section.

Rats received knife-cuts to the dorsal fornix or sham-operations. Half of the animals from each group were injected with clonidine (0.01 mg/kg) and the others with saline before each daily trail of a 10-trial radial 8-arm maze task. The number of choices before the first repetition and the run time were used as performance indices. Lesioned rats were significantly impaired in the acquisition of this task. Clonidine-treated rats, lesioned or not, had an acquisition profile indistinguishable from that of sham-operated saline-injected rats, in spite of their increased run time. When tested one week after the last learning trial in a no-drug condition, lesioned rats treated with clonidine throughout learning maintained a high level of performance during the 5-day retraining phase. A parallel analysis of theta rhythms recorded in an independent group of rats placed in equivalent treatment and/or lesion conditions was then performed. Preoperatively, clonidine injections decreased theta frequency during both alert immobility and movement. Partial fornix lesions produced an increase in theta frequency. Finally, clonidine in fornix-damaged rats decreased theta frequency, thus reinstating the postoperative values at a level statistically no different from that recorded preoperatively. The role of clonidine in restoring the function of the septo-hippocampal input in partially fornix-damaged rats through a noradrenergic modulation of hippocampal acetylcholine release is discussed.

Acetylcholinesterase↗
PubMed2004

DNA targeting of rhinal cortex D2 receptor protein reversibly blocks learning of cues that predict reward.

When schedules of several operant trials must be successfully completed to obtain a reward, monkeys quickly learn to adjust their behavioral performance by using visual cues that signal how many trials have been completed and how many remain in the current schedule. Bilateral rhinal (perirhinal and entorhinal) cortex ablations irreversibly prevent this learning. Here, we apply a recombinant DNA technique to investigate the role of dopamine D2 receptor in rhinal cortex for this type of learning. Rhinal cortex was injected with a DNA construct that significantly decreased D2 receptor ligand binding and temporarily produced the same profound learning deficit seen after ablation. However, unlike after ablation, the D2 receptor-targeted, DNA-treated monkeys recovered cue-related learning after 11-19 weeks. Injecting a DNA construct that decreased N-methyl-d-aspartate but not D2 receptor ligand binding did not interfere with learning associations between the cues and the schedules. A second D2 receptor-targeted DNA treatment administered after either recovery from a first D2 receptor-targeted DNA treatment (one monkey), after N-methyl-d-aspartate receptor-targeted DNA treatment (two monkeys), or after a vector control treatment (one monkey) also induced a learning deficit of similar duration. These results suggest that the D2 receptor in primate rhinal cortex is essential for learning to relate the visual cues to the schedules. The specificity of the receptor manipulation reported here suggests that this approach could be generalized in this or other brain pathways to relate molecular mechanisms to cognitive functions.

Animals↗
PubMed1975

Effects of diagnostic ultrasound irradiated during foetal stage on emotional and cognitive behaviour in rats.

Our previous work demonstrated that the prenatally irradiated ultrasound of even a low-intensity might affect the functional development of the brain of offspring in rats. In the present study, in order to investigate the emotional and cognitive behaviour of offspring of rats that received the irradiation of a diagnostic ultrasound on the 9th day of gestation, the following three experiments were carried out: 1) The emotional reactivity of the offspring was measured by the open-field technique. 2) The same reactivity was further evaluated in terms of the excape response from electroshock. 3) The cognitive function of the offspring was assessed through the discrimination learning and the discrimination reversal learning. The offspring of irradiated rats showed significantly more distinct vocalization response to handling in the open-field test and significantly more distinct escape response from the electroshock, when compared with the two control rats (untreated control and sham-irradiated control). From these findings it may be suggested that the emotional behaviour in rats can be influenced by a low-intensity ultrasound irradiated during foetal stage. On the other hand, as for the cognitive behaviour, the results of the present study suggest no adverse effect on it.

Animals↗
PubMed1993

Reversal of learned helplessness by chronic lithium treatment at a prophylactic level.

1. The effect of chronic lithium (Li) administration in a learned helplessness (LH) model was investigated. Female Wistar rats (190-210 g) received either tap water ad libitum (N = 56) or 20 mM LiCl (N = 63) in the drinking water or were water restricted (35% based on lower liquid intake of rats receiving lithium, N = 40) for 30 days. On the 28th day, each of these groups was divided into three subgroups which received escapable (ES), inescapable (IS) or no shock (NS) treatment in shuttle boxes. All groups were submitted to the escape test on the 29th day and sacrificed on the 30th day, when blood samples were taken for measurement of serum lithium, sodium and potassium concentrations. 2. The NS group had lower serum Li levels (0.36 +/- 0.06, N = 15) than the ES (0.46 +/- 0.07, N = 15) or IS group (0.44 +/- 0.09, N = 25). The Li-pretreated group subjected to IS had a more effective escape performance than the IS group under water restriction and showed the same behaviour as animals not submitted to shocks. 3. We conclude that chronic treatment with Li at a serum level of 0.44 +/- 0.09 mEq/l prevents learned helplessness in rats. These results corroborate the validity of the use of this model for the assessment of the capacity of Li to protect against some depressive episodes.

Animals↗
PubMedDate not supplied

Reversal of motor learning in the vestibulo-ocular reflex in the absence of visual input.

Motor learning in the vestibulo-ocular reflex (VOR) and eyeblink conditioning use similar neural circuitry, and they may use similar cellular plasticity mechanisms. Classically conditioned eyeblink responses undergo extinction after prolonged exposure to the conditioned stimulus in the absence of the unconditioned stimulus. We investigated the possibility that a process similar to extinction may reverse learned changes in the VOR. We induced a learned alteration of the VOR response in rhesus monkeys using magnifying or miniaturizing goggles, which caused head movements to be accompanied by visual image motion. After learning, head movements in the absence of visual stimulation caused a loss of the learned eye movement response. When the learned gain was low, this reversal of learning occurred only when head movements were delivered, and not when the head was held stationary in the absence of visual input, suggesting that this reversal is mediated by an active, extinction-like process.

Animals↗
PubMed2003

1439 MHz pulsed TDMA fields affect performance of rats in a T-maze task only when body temperature is elevated.

This study sought to clarify the effects of exposure to electromagnetic waves (EMW) used in cellular phones on learning and memory processes. Sprague-Dawley rats were exposed for either 1 h daily for 4 days or for 4 weeks to a pulsed 1439 MHz time division multiple access (TDMA) field in a carousel type exposure system. At the brain, average specific absorption rate (SAR) was 7.5 W/kg, and the whole body average SAR was 1.7 W/kg. Other subjects were exposed at the brain average SAR of 25 W/kg and the whole body average SAR of 5.7 W/kg for 45 min daily for 4 days. Learning and memory were evaluated by reversal learning in a food rewarded T-maze, in which rats learned the location of food (right or left) by using environmental cues. The animals exposed to EMW with the brain average SAR of 25 W/kg for 4 days showed statistically significant decreases in the transition in number of correct choices in the reversal task, compared to sham exposed or cage control animals. However, rats exposed to the brain average SAR of 7.5 W/kg for either 4 days or for 4 weeks showed no T-maze performance impairments. Intraperitoneal temperatures, as measured by a fiber optic thermometer, increased in the rats exposed to the brain average SAR of 25 W/kg but remained the same for the brain average SAR of 7.5 W/kg. The SAR of a standard cellular phone is restricted to a maximum of 2 W/kg averaged over 10 g tissue. These results suggest that the exposure to a TDMA field at levels about four times stronger than emitted by cellular phones does not affect the learning and memory processes when there are no thermal effects.

Animals↗
PubMed1998

Altered spatial learning and memory in mice lacking the mGluR4 subtype of metabotropic glutamate receptor.

The glutamate analog, L-2-amino-4-phosphonobutyric acid (L-AP4) is a selective agonist for several members of the metabotropic glutamate receptor (mGluR) family. Activation of presynaptic mGluRs by L-AP4 causes a suppression of synaptic transmission in the central nervous system. In this study, the role of 1 subtype of mGluR in the nervous system was investigated by analyzing mutant mice lacking the L-AP4-sensitive receptor, mGluR4. Experiments designed to probe hippocampal function showed no impairments in acquisition of spatial learning in the water maze task. However, in a spatial reversal learning task, the mutant mice exhibited significantly accelerated learning performance. Furthermore, in a probe trial administered 6 weeks posttraining, these mice showed impaired spatial accuracy. The results suggest that the mutant mice differed in their ability to learn and integrate new spatial information into previously formed memory traces and that their use of stored spatial information also was altered. Thus, the presynaptically expressed mGluR4 plays a role in the processing of spatial information.

Analysis of Variance↗
PubMed1996

Neural substrates of discriminative avoidance learning and classical eyeblink conditioning in rabbits: a double dissociation.

In a previous study, lesions of the deep cerebellar nuclei blocked classical eyeblink conditioning, but did not impair discriminative avoidance learning in rabbits. Here, was also found previously, lesions of the anterior and medial dorsal thalamic nuclei severely impaired discriminative avoidance learning. However, these lesions had no impact on discriminative eyeblink conditioning or reversal learning. These results complete the demonstration of a double dissociation, indicating distinct neural substrates for the acquisition of these learned behaviors. It is proposed that the two learning circuits identified by these studies mediate, respectively, acquisition of specific adaptive reflexes and whole-body, voluntary goal-directed movements.

Animals↗
PubMed1985

Alternation behavior, spatial discrimination, and reversal disturbances following 6-hydroxydopamine lesions in the nucleus accumbens of the rat.

The effects of dopaminergic depletion of the nucleus accumbens was tested in various behavioral tasks such as alternation, spatial discrimination, and reversal learning, and in an extinction paradigm in a T maze. Animals with lesions showed impairment of spontaneous alternation behavior, disturbances in the acquisition of spatial discrimination, and great difficulty in reversing previously learned habits. In the extinction phase, experimental animals are unable to adjust their behavior, and continue to choose the previously reinforced arm of the T maze. It is suggested that the nucleus accumbens plays an important role in the transition of motivation into action, and that dopamine has a facilitatory influence on the mediation of these processes.

Animals↗