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PubMed2001

Protective effect of nimodipine against cerebral injury induced by subacute carbon monoxide intoxication in mice.

AIM: To study the effects of nimodipine on delayed cerebral injury in mice from subacute carbon monoxide (CO) exposure. METHODS: Mice were exposed to CO (100 mL/kg, ip) once a day, continuously for 7 d. After 7-d CO-exposure, mortality in mice, changes in learning ability and memory using passive avoidance test, the pathomorphologic observation of brain tissue slices, and changes of monoamine oxide (MAO)-B activities in cerebral tissue were studied. Nimodipine was administered 30 min before CO-exposure every time. RESULTS: The preadministration of nimodipine decreased the mortality in mice, almost reversed the impairment of learning and memory function, prevented the hippocampal neurons against delayed death and blunted the rise of MAO-B activity after subacute CO poisoning of mice. CONCLUSION: Pretreatment with nimodipine markedly prevented mice from delayed encephalopathy after CO poisoning.

Animals↗
PubMed2000

Protective effects of fructose-1,6-diphosphate against cerebral injury induced by subacute carbon monoxide intoxication in mice.

AIM: To study the effects of fructose-1,6-diphosphate (FDP) on delayed cerebral injury in mice from subacute carbon monoxide (CO) exposure. METHODS: Mice were exposed to CO (100 mL/kg i.p.) once a day, continouUsly for 7 d. After 7-d CO-exposure, mortality of mice, changes in learning ability and memory using passive avoidAnce test, the pathomorphologic observation of brain tissue slices, and changes in monoamine oxide (MAO)-B activities in cerebral tissue were studied. FDP was administrated 30 min before CO-exposure every time. RESULTS: The preadministration of FDP markedly decreased the mortality of mice, almost reversed the impairment of learning and memory function, prevented the cells from delayed death in hippocampal neurons and blunted the rise in MAO-B activity after subacute CO poisoning of mice. CONCLUSION: FDP pretreatment markedly prevented mice from delayed encephalopathy after CO poisoning.

Animals↗
PubMed1997

Reversal of sterilisation by the railroad technique.

OBJECTIVE: To show that a simple, easily learned and relatively inexpensive method of reversal of sterilisation provides good results. DESIGN: Retrospective observational study. SETTING: An NHS Trust Hospital. SAMPLE: Sixty-seven women aged 19 to 39 years who underwent reversal of sterilisation between January 1984 and December 1993. MAIN OUTCOME MEASURES: Pregnancy rate following reversal; rate of ectopic pregnancy. RESULTS: Thirty-four women (51%) had intrauterine pregnancies after reversal of sterilisation; intrauterine pregnancy rate in women who had been sterilised with rings or clips was 64%. Five women (7.5%) had ectopic pregnancies. CONCLUSION: This technique provides results that compare favourably with those of microsurgery. It offers hope to couples who do not meet the restrictive criteria for microsurgery and in vitro fertilisation and should appeal to purchasing authorities.

Abortion, Spontaneous↗
PubMed2000

Can squirrel monkeys (Saimiri sciureus) learn self-control? A study using food array selection tests and reverse-reward contingency.

Eight squirrel monkeys (Saimiri sciureus) were presented with 2 stimulus arrays, namely 1 and 4 pieces of food, but they received only the array other than the one they reached for. In this reverse-reward condition, all monkeys initially showed a strong preference for the larger array. One monkey learned to reach toward the smaller array when a large-or-none reward contingency was applied (i.e., no reward followed a reach toward the larger array, but this array was given for a reach toward the smaller array). When correction trials and time-out were added to the large-or-none procedure, all remaining monkeys except 1 learned this form of self-control. Performance was maintained when correction trials were discontinued, the original reverse-reward condition was rerun, and novel array-size pairs were presented. This study demonstrates one form of self-control in a New World primate and shows the reverse-reward procedure to be a potentially valuable method for assessing species and individual differences in self-control and numerosity-related abilities.

Animals↗
PubMed1997

What is the role of the corpus callosum in intermanual transfer of motor skills? A study of three cases with callosal pathology.

Intermanual transfer for a skilled motor task was studied in two patients with total callosal agenesis, and one with an acquired partial callosal lesion and clinical evidence for disturbed transfer of motor signals. Patients had to draw meaningless figures with one upper extremity (original learning, OL) and to reproduce their mirror-reversals thereafter with the other side (transfer learning, TL). Both directions of intermanual transfer were tested in two conditions, that is, between either proximal or distal muscle groups. Transfer was evaluated by comparing OL and TL performance at the same effector. The main variable of interest was movement time during the first eight trials of OL and TL. All three patients displayed a significant benefit for transfer from the dominant to the non-dominant hand but not vice versa during proximal motor activity. When compared with the performance of healthy subjects tested in almost identical conditions in a previously reported study, the proximal transfer behavior was found to be similar for all patients and the normal group. Although patients exhibited no significant benefit for distal transfer, their non-dominant-to-dominant distal transfer was above the normal range. The similar transfer pattern of the patients and healthy subjects when using proximal musculature suggests that proximal transfer may be subserved by identical extracallosal pathways, most probably by the ipsilaterally descending motor systems. Since non-dominant-to-dominant distal transfer was found to be disadvantageous in healthy subjects, the patients' relative superiority in this condition may reflect missing callosal influences of an inhibitory nature.

Adult↗
PubMedDate not supplied

Temporally graded retrograde amnesia following separate and combined lesions of the perirhinal cortex and fornix in the rat.

The involvement of the perirhinal cortex and the fornix in retrograde and anterograde amnesia in the rat was investigated in this experiment. Male Sprague-Dawley rats were trained on a series of five visual discrimination problems at distinct time intervals prior to receiving bilateral, electrolytic lesions of the perirhinal cortex or the fornix, combined lesions of both these structures, or sham operations. Following recovery from surgery, rats were retested on the preoperatively learned discrimination problems, as well as learning a new discrimination and discrimination reversal. Results indicated that all animals with lesions exhibited temporally graded retrograde amnesia, whereby memories acquired in the recent past (1-3 weeks) were impaired, and memories acquired in the remote past (6-8 weeks) were spared. There was no difference in the magnitude of retrograde amnesia between the three lesion groups. Animals in the perirhinal, fornix, and combined lesion groups were able to learn a new discrimination problem at a rate comparable to control rats; however, the animals with lesions were impaired at learning the discrimination reversal. The perirhinal, fornix, and combined lesion animals also exhibited a significantly faster forgetting rate over a 2-week retention interval than control rats. These results suggest that medial temporal structures including the perirhinal cortex and the fornix are involved in the consolidation of mnemonic information and that their involvement in this process occurs over a discrete period of time.

Amnesia↗
PubMed1978

Single unit activity in cat prefrontal and posterior association cortex during performance of spatial reversal tasks .

Relationships between the performance of complex learning tasks and the firing patterns of single unites in prefrontal and posterior association areas of the neocortex were studied in 9 cats. Recording data from 2 additional cats served as controls for sensory and motor aspects of the tasks employed. During recordings, animals sat in a box, their heads fixed to a stereotaxic instrument, and performed a non-sensory spatial reversal or delayed-alternation task by pressing 1 of 2 lateralized retractable levers. Units obtained were classified into 5 basic types according to their correlation with aspects of the tasks. The first 3 types were related directly to sensory, motor and motivational aspects of the tasks. The fourth type was named associative, as it contained units which changed firing rates in advance or as a consequence of environmental events, rather than in direct relation. Discharge changes of units of the fifth type were rated as non-specific or non-specifiable. Between recording areas and tasks a striking similarity of unit firing patterns was obtained. Differences were observed only between the reactivity of polymodal cells in prefrontal and in posterior fields, and in the proportions of units revealing mnemonic and motor response aspects. It was concluded that a considerable functional overlap between prefrontal and posterior association areas of the cat with respect to processing of complex learning tasks exists on the single neuron level.

Acoustic Stimulation↗
PubMed2003

Flumazenil and tacrine increase the effectiveness of ondansetron on scopolamine-induced impairment of spatial learning in rats.

RATIONALE: Cholinergic receptor blockade produces memory deficits in animal models. These deficits can be prevented by 5-HT3 receptor antagonists, such as ondansetron, which increases acetylcholine release. We investigated the effects on cognitive performance of combined treatments of ondansetron with either flumazenil, a GABA(A) receptor benzodiazepine site antagonist, or tacrine, a cholinesterase inhibitor, which are also able to prevent scopolamine-induced cognitive impairment. METHODS: Spatial learning and memory was assessed by studying the effects of single and combined treatments on acquisition and retention of the Morris water maze task in rats. RESULTS: Scopolamine (0.6 mg/kg) induced significant learning and retention deficits. Both ondansetron (0.1 microg/kg) and tacrine (3 mg/kg) partially prevented the scopolamine-induced learning deficit. A full reversal was only found after the combined treatment of ondansetron with flumazenil (10 mg/kg) and also after tacrine in combination with ondansetron. Likewise, scopolamine-induced retention deficit was fully counteracted by the combined treatment of ondansetron with either flumazenil or tacrine, and only partially by any of the single treatments tested. CONCLUSIONS: The scopolamine-induced impairment of learning and retention in the water maze is fully prevented by ondansetron when given in combination with either flumazenil or tacrine, suggesting that both combined treatments result in a potentiated cholinergic function and may constitute the basis of a new therapy for cognitive disorders.

Animals↗
PubMed1989

Intervention of the lateral and central amygdala on the association of visual stimuli with different magnitudes of reinforcement.

Male rats received either kainic acid (KA) or sham lesions bilaterally into the lateral and central amygdala or were assigned to an unoperated control group. After the postoperation recovery period all lesioned and unoperated animals were tested for the ability to master a visual-stimulus/magnitude-of-reinforcement discrimination. Retention of the discrimination learning was evaluated 24 h later for the original and reversal problems. The lateral and central amygdala lesions differently affected the acquisition of a visual-stimulus/magnitude-of-reinforcement discrimination and did not impair its retention. The lateral amygdala-lesioned group showed a significantly poorer performance in discrimination learning than all the other groups. Its performance was even poorer than that of the central amygdala-lesioned group. The contribution of lateral and central amygdala in the major components of a visual-stimulus/magnitude-of-reinforcement discrimination is discussed. In order to know how the amygdala is involved in the association of sensorial stimuli with reinforcement, we suggest that the specific contribution of its individual nuclei in the detailed components of such an association be studied.

Amygdala↗
PubMed1999

The effect of excitotoxic hippocampal lesions on simple and conditional discrimination learning in the rat.

The effect of excitotoxic lesions of the hippocampus on acquisition and reversal of simple and conditional tasks was investigated using a Y-maze. Hippocampal-lesioned rats were severely impaired on acquisition and reversal of a conditional visuo-spatial task (where different pairs of visually distinctive choice arms indicated whether a left or right arm choice was correct on that trial) and were unable to acquire a visuo-visual conditional discrimination (where the appearance of the start arm indicated which of the visually distinctive choice arms was correct irrespective of their left/right position). They were not impaired on acquisition or reversal of a simple spatial left/right discrimination task (where all arms had the same visual appearance) nor on acquisition of a visual discrimination (where the correct, visually distinctive, choice arm varied in its left/right position). Hippocampal-lesioned rats were, however, impaired on reversal of this visual discrimination task and on acquisition and reversal of another visual discrimination task in which the visually distinctive choice arms were less different from each other than in the first version of this task. The degree of impairment in the lesioned rats was related to task difficulty for the sham-operated rats and was not specific to tasks requiring spatial choices, visual discrimination or conditional responding. The impairment on conditional tasks was greater than the impairment on those non-conditional tasks which happened to be matched for task difficulty for the sham-operated rats, suggesting that the conditional demand may target the function of the hippocampus rather closely. Statistically worse than chance performance by hippocampal-lesioned (and sham-operated) rats at the beginning of reversal testing, which was given 24 h after achieving criterion on acquisition of that task, indicated that hippocampal-lesioned rats simultaneously exhibited good memory but impaired learning for the type of information required for those tasks.

Animals↗
PubMed1986

Classical conditioning rapidly induces specific changes in frequency receptive fields of single neurons in secondary and ventral ectosylvian auditory cortical fields.

To determine if learning-induced changes in the response of auditory cortical neurons to a conditioned stimulus (CS) reflect general changes in cellular excitability or alterations in signal processing that are specific to that stimulus, we determined frequency receptive fields (FRFs) of single neurons in secondary and ventral ectosylvian auditory fields of the cat during classical conditioning. Associative changes in FRFs of most cells were specific to the frequency of the CS, established rapidly and reversed by extinction. Thus, learning causes specific changes in cortical processing of sounds whose significance is acquired.

Animals↗
PubMed1968

An experimental analysis of linguistic development: the productive use of the plural morpheme.

Operant conditioning procedures were used to establish a generative use of the plural morpheme in the speech of a severely retarded girl. During training trials, reinforcement was presented contingent upon correct imitation of singular and plural verbalizations by the experimenter, in response to objects presented to the subject singly and in pairs. A generative productive plural usage resulted, the girl correctly labeling new objects in the singular or plural without further direct training relevant to those objects. After establishing the singular/plural usage, the contingencies were reversed (reinforcement of plural responses to single objects, and vice-versa). This produced a corresponding reversal of response by the child. The original usage was then recovered by returning to the previous contingencies. A second experiment analyzed certain error responses occurring during the first experiment, and further probed the generative nature of the subject's plural usage. It was found that errors were somewhat more likely to occur in the pluralization of words ending in vowels than of words ending in consonants. Furthermore, several words whose plurals had been learned according to the reversed plural rule, when examined later during reinforcement of normal plural usage, were found then to exemplify the normal rule being reinforced, yet without direct training.

Journal Article↗
PubMed1996

Befloxatone, a new reversible and selective monoamine oxidase-A inhibitor. II. Pharmacological profile.

The pharmacological profile of befloxatone, a reversible, selective and competitive inhibitor of monoamine oxidase-A has been investigated in rodents. In mice, befloxatone was more active at potentiating generalized tremors induced by L-5-hydroxytryptophan (ED50, 0.21 mg/kg p.o.) than phenylethylamine-induced stereotypies (ED50, 58 mg/kg p.o.), indicating a very high in vivo selectivity for inhibition of the A form of monoamine oxidase. Befloxatone showed potent activity in behavioral models in rodents predictive of antidepressant activity (forced swimming test, learned helplessness and reserpine reversal) with minimal effective doses of 0.1 to 0.2 mg/kg p.o. In these tests, befloxatone was much more potent (10- to 500-fold) than reference antidepressant compounds (reversible and irreversible monoamine oxidase inhibitors and monoamine reuptake inhibitors). In rats, befloxatone increased rapid eye movement sleep latency and decreased rapid eye movement sleep duration, without rebound effects. Potential anxiolytic activity was observed in the elevated-plus maze test in rats (minimal effective dose, 1-2 mg/kg p.o.). Befloxatone had no effect on motor performance, did not induce sedative or stimulant activity up to doses of 200 mg/kg p.o. and was devoid of anticholinergic activity in mice. Interaction studies with p.o. dietary tyramine (12 mg/kg), carried out in freely moving rats, demonstrated that, in contrast to irreversible monoamine oxidase inhibitors, befloxatone did not potentiate the pressor effect of this amine in the range of doses which showed pharmacological activity in antidepressant behavioral models. Furthermore, of the compounds tested (moclobemide, brofaromine, nialamide and phenelzine), comparison of doses active in antidepressant models and doses potentiating the pressor effects of tyramine demonstrated that befloxatone had the best therapeutic index. The results suggest that befloxatone will show clinical antidepressant activity at low doses and will be devoid of the side effects associated with irreversible monoamine oxidase inhibitors.

Animals↗