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Antagonism of skin conductance response (SCR) habituation during iterative photostimulation in mice: habituation test - a new psychopharmacological method for detecting and quantifying enhancement of psychic activity.

A method (habituation test) for studying habituation of the palmar skin conductance response (SCR) during iterative photostimulation in mice is described. Twenty drugs known for their CNS stimulant activity and/or beneficial action on learning were tested for their antagonism toward habituation. With most of the drugs tested, the delay in SCR extinction was dose-dependent. From the corresponding regression equations, the standard delaying doses were computed and used for classification. Fenozolone was the most active product. In descending order follow dexamphetamine and piracetam, then other amphetamines. Locomotor activity tests were run in parallel with habituation tests and the two sets of results compared. Reliability of habituation test was checked. The responsiveness of the test and the significance of the results are discussed. The applicability of the habituation test in psychopharmacological research is argued by its sensitivity to piracetam, whose nootropic activity is not detectable by classic behavioral methods. The habituation test makes it possible to test drugs for their effects on the maintenance of attention during monotonous stimulation and, more generally, for their psychic enhancement activity whatever the mechanism involved. It is thus likely to be a suitable test for nooanaleptics (in the broad meaning of the term).

Animals

Habituation and transfer during sleep in cats.

In order to test the concept of "sleep learning", cats were exposed to habituation treatment of auditory stimuli during different stages of the sleep-waking cycle. While it was possible to demonstrate that habituation to an auditory stimulus can take place in paradoxical sleep (PS) and slow-wave sleep (SWS) as well as during periods of wakefulness, it was not always possible to demonstrate a transfer of habituation from the training period to other periods. A complete transfer of habituation occurred between the two sleep periods (PS and SWS); a partial transfer of habituation occurred between the waking period and both of the two sleep stages (PS and SWS), but only a minimal transfer of habituation was found between any one of the sleep stages and the waking period. When the cats were able to transfer the habituation, they also were able to discriminate between the habituating tone and a novel tone. The findings that only minimal transfer of habituation could occur between each of the sleep stages and the waking period do not lend support to the concept of "sleep learning".

Animals

Some observations on habituation of the flexor reflex in the rat: the influence of strychnine, bicuculline, spinal transection, and decerebration.

The involvement of inhibition in habituation of the flexor reflex was investigated in intact, spinal, and decerebrate rats. Strychnine and bicuculline were administered in order to determine the contribution of certain forms of central inhibition to the development of habituation. Both strychnine and bicuculline reduced habituation in the intact rat but did not do so in the spinal preparation. Strychnine, in fact, caused a facilitation of habituation in the spinal rat. The impairment of habituation by strychnine was related to the intensity of stimulation used to elicit the reflex. Thus, the effect of strychnine was only demonstrable when relatively high intensities were used. Flexor reflex habituation was shown to be more pronounced in the decerebrate than in the spinal preparation. This difference could be demonstrated only when stimuli of high intensity were given. It is concluded that, in the absence of supraspinal influences, habituation of the flexor reflex does not require inhibitory mechanisms. However, inhibition may play a role in habituation of the component of the reflex that utilizes descending influences.

Animals

Individual differences in habituation of human physiological responses: a review of theory, method, and findings in the study of personality correlates in non-clinical populations.

Studies up to 1976 of the relationship between psychometrically defined dimensions of personality and individual differences in habituation of EEG and autonomic responses were examined. Attention was confined to reports employing persons who were not diagnosed as suffering from mental disorder, institutionalized for this reason of for delinquent or criminal behaviour. The dimensions of extraversion and anxiety were most frequently found to be implicated in predictions about individual differences in response habituation, though no consistent rationale for these predictions was identified. Methodological problems involved in studying the predictions were considered, and a number of factors relating to measurement of personality and habituation and the experimental conditions under which response habituation is studied were suggested as possible sources of confounding. A survey of the empirical literature led to the conclusions that anxiety as defined by the Manifest Anxiety Scale is related to habituation of the finger vasomotor response but probably not to habituation of the electrodermal response, while extraversion, as defined by Eysenck's scale, is related to habituation of the electrodermal response. For other scales and other dimensions, including cognitive factors, the available data are inconsistent or too meagre to permit conclusions being drawn. It is suggested that future research be directed to a systematic investigation of the conditions under which personality factors contribute significantly to individual differences in response habituation, rather than seek to identify general relationships.

Arousal

Habituation and the human evoked potential.

Habituation of human scalp-recorded cerebral evoked potentials was studied in response to auditory and visual repetitive stimuli of different intensities. Changes in magnitudes of evoked potentials with stimulus repetition were examined according to the parametric characteristics of habituation, generalization, and dishabituation. In addition, tests of the predictions of two theories of habituation were made regarding the degree and direction of intensity generalization of habituation. Both auditory and visual evoked potentials exhibited decrements in response magnitudes across the repetitive stimuli consistent with the parametric criteria of habituation. Early evoked potential peak components showed a pattern of intensity generalization of habituation consistent with the predictions of the dual-process theory of habituation. Intensity generalization of late evoked potential peak components occurred in a manner more consistent with the predictions of the stimulus comparator theory of habituation. These results provide further evidence that evoked potentials can be used as electrophysiological indexes of plasticity in humans.

Adult

L9 modulation of gill withdrawal reflex habituation in Aplysia.

Repeated tactile stimulation of the siphon in Aphysia normally results in habituation of the gill withdrawal reflex and a concomitant decrease in the amplitude of the excitatory synaptic input ot gill motor neurons in the abdominal ganglion. It was found, however, that induced low-level tonic activity in motor neuron L9, which does not itself elicit a gill withdrawal movement, prevented habituation of the reflex from occurring. Further, in preparations already habituated, this tonic low-level activity brought about a reversal of habituation. Although tonic L9 activity prevented the occurrence of habituation or brought about its reversal, it did not interfere with the synaptic decremental process which normally accompanies gill reflex habituation. Motor neurons L7 and LDG1 were found not to possess this ability of L9 to modulate gill reflex habituation. Evidence suggests that L9's modulatory effect is mediated in the periphery, in the gill and not centrally in the abdominal ganglion.

Animals

[Characteristics of habituation in visceral systems].

In anesthetized and immobilized cats, habituation of evoked responses to repeated stimulation of the splanchnic nerve occurred in the cerebral cortex. Upon cessation of the stimulation, the habituation waned spontaneously (spontaneous recovery). The rate of spontaneous recovery depended on number of habituating stimuli (effect of "below-zero"). Repeated series of habituation training produced a more rapid habituation of EPs (potentiation of habituation). An extrastimulus to cutaneous or splanchnic nerve leads to recovery of the evoked response (dehabituation or sensitization). Repeated application of the dehabituating stimulus produced a progressively lesser sensitization (habituation of dehabituation).

Animals

Ontogenesis of spontaneous activity and habituation of activity in the rat pup.

Individual components of activity and habituation of activity were determined throughout the 1st month of life in the rat pup. Total activity increased from 25% at 8 days of age to 68% at 22 days before declining to 49% at 26 days. Total slight activity (predominantly sniffing) increased to a maximum of 33% at 15 days whereas total very active behavior (predominantly ambulation) reached its maximum of 38% at 22 days. Habituation of activity expressed as the mean slope of decrement of activity over the 1st 30 min of the observation period was observed in rats as young as 8 days of age. By 12 days, habituation of total activity had increased significantly reflecting a 3-fold increase ihabituation of slight activity, an effect observed at 15 days as well. However, by 19 days the slope of activity decrement had declined to half of its 15-day value, indicating an impairment of habituation and reflecting the attenuation of very active behavior, predominantly ambulation. This decline in habituation continued through 22 days but by 26 days habituation of activity had increased again reaching a maximum for the 1st month of postnatal life. Our results suggest that the phenomenon of behavioral arousal observed in the developing rat pup 19 days of age reflects an inability of the organism to modulate his activity as effectively as the 15-day- or 26-day-old animal.

Animals

Analysis of the habituation-like changes in transmission in the temporodentate pathway of the rat.

Habituation-like decrements in extracellular measures of synaptic activation (population EPSP) and cell discharge (population spike) were analyzed in the dentate gyrus of the rat following repetitive low-frequency stimulation of the medial and lateral entorhinal cortex. Stimulation of either subdivision of the entorhinal projection system resulted in comparable habituation-like response decrements with similar stimulation regimens. However, habituating stimulation of one subdivision did not result in decreased responsiveness to stimulation of the other. Repetitive low-frequency stimulation or even a single pulse delivered to either subdivision did, however, result in a potentiation of granule cell discharge in response to stimulation of the other subdivision (a form of heterosynaptic potentiation). This heterosynaptic potentiation of granule cell discharge was not accompanied by any increase in the extracellular EPSP. Comparisons of the relationship between the population EPSP and population spike before and during habituating stimulation revealed changes in cell discharge in response to the habituating stimulus which could not be accounted for by changes in synaptic activation alone. The results suggest that repetitive activation of the temporodentate pathway alters granule cell output as a result of two processes, a habituation-like decrement in synaptic activation, and a potentiation of granule cell discharge as a consequence of prior activation.

Afferent Pathways

Ontogeny of spontaneous blinking and of habituation of the blink reflex.

Habituation of the blink reflex to glabellar percussion was examined in 164 infants and children from ages 2 days to 18 years and in 18 adults aged 18 to 50 years. Spontaneous blink rates were measured in 269 children and 179 adults. The mean number of glabellar taps required for habituation of the blink reflex increased from 2.7 (SD 1.2) at 0 to 2 months of age to a peak of 13.3 (SD 5.6) at age 3 to 4, remained at more than 10 until age 6, after which a rapid decline occurred, reaching the adult level of 2 to 5 blinks to habituation at age 12 years. The mean rate of spontaneous blinking was less than 2 per minute in early infancy and increased steadily during childhood up to age 14 or 15. The inverse relationship of spontaneous blink rate and number of blink reflexes to habituation in early childhood and in disorders of dopamine transmission suggests that spontaneous blink rate and habituation of the blink reflex reflect maturation and integrity of dopaminergic circuits in the brain.

Adolescent

Effects of N,N-dimethyltryptamine on behavioural habituation in the rat.

The processes involved in habituation and the various ways drugs might affect habituation are discussed. Exploration was measured in a holehoard and N,N-Dimethyltryptamine (DMT, 4 mg/kg) profoundly reduced the level of exploration, precluding any conclusions about the rate of habituation with this dose. However, both 2 and 4 mg/kg doses prevented the 24-hr retention of habituation of exploration. DMT (2 and 4 mg/kg) did not reduce the initial distraction to a tone stimulus, but the rate of habituation and its 24-hr retention was impaired.

Animals

ACTH, but not corticosterone impairs habituation and reduces exploration.

The habituation of an orienting response to auditory stimuli was impaired in rats by the administration of ACTH1-24. This impairment is unlikely to be due to the action of corticosterone because of the time course of the effect, because injected corticosterone had no effect on hibituation and because the peptide fragment ACTH4-10, which does not release corticosterone, also impaired habituation. Both ACTH1-24 and ACTH4-10 reduced the level of exploration measured in a holeboard, but corticosterone had no significant effect. However ACTH did not impair habituation and exploration, thus providing further evidence that there are different mechanisms underlying habituation of orienting and habituation of exploration.

Adrenocorticotropic Hormone

Ascending 5-HT pathways and behavioural habituation.

Microinjections of 5,7 -dihydroxytryptamine into both the dorsal and median raphe nuclei resulted in 70-85% depletions in striatal and hippocampal 5-HT concentrations but did not affect habituation of orienting in the lick-distraction test, habituation of activity in an open-field or habituation of exploration in the holeboard test. Lesioned animals were hypoactive in the latter two tests and defaecated more than control rats in the open-field suggesting an increase in emotionality or fear. Rats with selective 5,7 -dihydroxtryptamine lesions of either the dorsal or the median raphe nucleus also showed no impairment of habituation of orienting or exploration. However, median raphe lesioned animals were hyperactive at some stages of the holeboard test. In contrast to previous studies, the results suggest intact ascending 5-HT pathways are not necessary for behavioural habituation of orienting, activity or exploration. Rather, 5-HT neurones may be involved in modulation of activity or responsiveness to aversive environments.

Acoustic Stimulation

The menstrual cycle and habituation.

A group of women were studied over two consecutive menstrual cycles, at about one week intervals. Twenty-one of these women had spontaneous ovulatory menstrual cycles, 6 women had anovulatory cycles, and 7 were regular users of oral contraceptives. All cycles were converted to classic 28 day cycles. On each visit, a record was obtained of the subject's galvanic skin responses (GSRs) to 21 successive auditory stimuli. It was found that, during ovulatory cycles, a marked change in the rate of habituation of the GSR occurred around day 14 and day 28. During days 1--14 the mean habituation point (number of GSR responses to sound before 3 successive nonresponses) was 12.4 SE 1.6. This dropped to 6.8 SE 1.6 during days 15--28 (2-tailed t test, p less than 0.001). This change was not found for women on oral contraceptives, who showed consistent habituation rates throughout the cycle (mean habituation point 7.2 SE 1.1). The evidence also suggested that women with anovulatory cycles differed from those with ovulatory cycles in that they did not show a chnage in their habituation point around midcycle.

Acoustic Stimulation

Protection from habituation of the crayfish lateral giant fibre escape response.

1. Habituation of the lateral giant fibre escape response in the crayfish to repetitive tactile stimuli is believed to result from homosynaptic depression at the first synapse of the reflex, between tactile afferents and interneurones. Normally, habituation of escape responses to repeated innocuous stimuli is presumed to be adaptive. Experiments reported here were undertaken to determine whether habituation would occur under circumstances when it would presumably be maladaptive - in particular, when tactile receptors are stimulated by an animal's own tail-flip movements.2. Experiments were carried out on the crayfish isolated abdominal nerve cord, which contains the lateral giant reflex pathway.3. Compound e.p.s.p.s elicited in the lateral giant by electrical stimulation of tactile afferents decline by from 25 to 36% over a series of eleven trials at 1/5 sec (control series).4. To determine whether such a decline would occur when sensory afferents are stimulated during a ;tail-flip', stimuli were given as in the control series but each stimulus occurred 20 msec after direct electrical stimulation of a medial giant or lateral giant escape-command fibre at which time tail flexion movements of an intact animal would be in progress. Under these conditions% e.p.s.p. decline over 11 trials at 1/5 sec was only 16-45% of that occurring on the control series.5. This protective effect starts at about 10 msec after escape command neurone firing, is maximal at 20 msec, and thereafter declines, remaining weakly detectable at 100 msec. This time course is commensurate with that required for execution of a tail-flip movement. Thus, sensory afferent-to-lateral giant transmission is protected from depression if stimuli occur when a tail-flip movement is or should be occurring.6. Giant fibre spikes do not superimpose facilitation upon a depressed reflex pathway, nor accelerate rate of recovery from depression; rather, protection is attributable to actual prevention of development of the depressed state.7. Protection was also examined at the first synapse of the reflex, where the depression responsible for habituation is believed to occur, by recording intracellularly in the largest of the first-order interneurones (interneurone A) of the pathway. In absence of protection, ten stimuli presented at 1/4 sec caused a mean decline of 32% in the e.p.s.p. in interneurone A. When such stimuli followed directly evoked escape command neurone firing by 20 msec this decline was reduced by 59-100%.8. We suggest that protection serves to prevent crayfish from habituating to stimuli produced by their own tail-flip movements.

Action Potentials

Dynamics of habituation in different cortical regions of the cat brain.

The dynamics of habituation in the rostral part of the parietal association region and also in the first and second somatosensory areas was studied by the evoked potentials (EP) method in cats anesthetized with chloralose (80-90 mg/kg) and immobilized with flaxedil. During repeated stimulation of the splanchnic nerve brief habituation of EP developed in the cortex. It corresponded in its basic features to habituation observed in other sensory systems. On comparison of the rates of development of habituation in the primary and secondary projection zones of the splanchnic nerve in the cortex differences were found: habituation developed more rapidly in the secondary projection zones. The functional importance of this phenomenon is discussed.

Animals

Multiple unit activity study of brain stem and limbic structures during environmental habituation and circadian rhythm.

Multiple unit activity (MUA) of brain stem, hypothalamic and limbic structures was studied during habituation to a novel environment and circadian rhythm in chronically implanted freely moving rats. MUA was analysed in the mesencephalic reticular formation (MRF), area hypothalami posterior (PH), basal nuclear group of amygdala (AMY), area septalis (SEPT), dorsal hippocampus (HIPP) and area hypothalami anterior (AH). It was found that in the novel environment MUA of all subcortical structures increased to a high level. During habituation MUA in each phase of wakefulness--sleep cycle decreased to stable low level both in brain stem and forebrain structures. Gradual decrease in MUA was characteristic to MRF, and a sharp decrease occured in AH and AMY. The environmental habituation proved to be a long lasting process in rat. During all phases of wakefulness--sleep cycle activity was significantly higher in the light period than in the dark, and MUA base level showed circadian variation both in brainstem and limbic structures. Close correlation was found between the actual MUA level and responsiveness to various sensory modalities both during habituation and circadian rhythm. The higher the MUA level, the higher the responsiveness, and a fall in activity was accompanied by decreased neuronal responsiveness.

Amygdala

Effects of parachlorophenylalanine and amphetamine on habituation of exploration.

Parachlorophenylalanine (PCPA, 400 mg/kg) retarded the habituation of exploration in the rat recorded over 3 successive days. A more detailed analysis showed that this was not due to any retention deficit, but was secondary to an impairment of habituation within each session. PCPA also disrupted the response of rats to a change of stimuli. (+)amphetamine (4 mg/kg) prevented exploration in the rat and a 2 mg/kg dose reduced exploration and impaired within-session habituation. (+)amphetamine (1 mg/kg) in mice impaired within-session habituation, without significantly reducing exploration. The nature of the deficits produced by these 2 drugs is discussed.

Animals