Level of neuroactive steroids in the brain and sex-related peculiarities of formation and extinction of conditioned reflex in rats

Sex-related peculiarities of dynamics of brain sex steroids in the process of learning and extinction of the conditioned reflex of passive avoidance have been studied in model experiment. Prior to learning of the conditioned reflex, female rats were found to be distinguished by manifestation of anxiety and fear as compared with male rats. At formation of the conditioned reflex, no significant sex-related differences were detected between males and females, whereas extinction of the conditioned reaction of passive avoidance in males occurred by 2–3 days faster than in females. At learning of conditioned reaction of passive avoidance, in sexually mature male rats there was revealed an increase of the testosterone content in various brain structures, especially in hippocampus and frontal cortex, while its level in blood plasma remained unchanged. Also shown was an elevation of estradiol concentration in female amygdale, whereas at extinction of the conditioned reaction of passive avoidance, a rise of estradiol values was noted in hippocampus and cingular cortex. At the same time, the testosterone level in blood plasma did not change, whereas after extinction of the conditioned reflex the estradiol concentration decreased statistically significantly. Different dynamics of changes of the sex steroid levels in brain and blood plasma can indicate a possibility of their formation in the nervous tissue. The performed correlation analysis confirms the concept of selective involvement of testosterone and estradiol of individual brain structures in realization of processes of learning and memory in sexually mature male and female rats.     

Level of neuroactive steroids in the brain, and gender-related differences in formation and decrease of conditioned reflex in rats

We investigated gender-related differences in dynamics of the brain sexual steroids during learning and the decrease of conditioned reflex in the modeling experiment. It was revealed that, before training to conditioned reflexes, females manifested a greater anxiety than males. Significant differences between males and females in formation of the conditioned reflex of passive avoidance were not revealed, whereas the conditioned response decrease were by 2-3 days faster in male rats than in females. It was revealed that there was an increase of testosterone content in various structures of the brain, especially in hippocampus and frontal cortex with its constant level in the blood plasma in learning conditioned response of passive avoidance in male adult rats. Also an increased estradiol concentration was found in females' amygdale, while increased value of estradiol was detected in hippocampus and the singular cortex in decrease of the conditioned response of passive avoidance. In blood plasma, the testosterone level was not changed, and the estradiol concentration was reduced significantly after the decreased conditioned reflex. Different dynamics of changes in the levels of sex steroids in the brain and the blood plasma can indicate a probability of their formation in nervous tissue. The correlation analysis confirms the conception about selective involvement of the brain's testosterone and estradiol in the specific structures in realization ofthe learning and memory processes in adult male and female rats.     

Significance of the relative position in space of associated stimuli for formation and performance of motor conditioned reflexes

In experiments on cats the rate of formation of conditioned reflexes to sound (running to the feeding trough) depended on the spatial interrelations of the paired stimuli: the closer the source of the conditioned signal to the feeding trough, the sooner the formation of the conditioned reflex. It has been assumed that during formation of a conditioned reflex the closing of connection between conditioned and unconditioned stimuli is also attended with the closing of connection between the spatial parameters of the paired stimuli. Experiments with inactivation through cold of the temporal area (cortical representation of the vestibular system) of one hemisphere have shown that such a connection is formed in central parts of the vestibular analyser. When the conditioned reflex is elaborated to one feeding trough, the connection is duplicated by both hemispheres; in reflexes to two feeding troughs (i.e. spatial choice) such connections are lateralized in each hemisphere.     

Reflection of the process of conditioned reflex formation in shifts of the steady potential level]

In chronic experiments on rabbits with non-polarizable electrodes shifts of steady potential level (SPL) are recorded from the brain surface during extinction of the orienting reaction and formation of a conditioned defensive reflex. During each of these processes they have their typical parameters and are respectively denoted by the author as: orienting (appearing in response to a new stimulus), conditioned (to a signal atimulus), unconditioned (to an electro-cutaneous stimulus) and trace SPL shifts (developing after stimuli pairing). Trace shifts are the earliest SPL shifts originating as a result of pairing. They are manifested more regularly, than conditioned ones, considerably exceed them in amplitude, may differ from them in their sign and reach maximum values in a few seconds after the pairing. It has been assumed that formation of conditioned temporal connections depends above all on the appearance of a new kind of activity, resulting from pairings and reflected in the SPL trace shifts. This activity possibly constitutes the neurodynamic and metabolic processes underlying memory consolidation.     

The characteristics of shuttle avoidance learning in spontaneously hypertensive and normotensive rats]

In spontaneously hypertensive (strain SHR) and normotensive (strain WKY) rats was studied the elaboration of conditioned reflex of active avoidance in shuttle box. In case when the shuttle box was divided by a partition the SHR rats learned worse than WKY rats. In shuttle chamber without partition the SHR rats, on the contrary, learned better that WKY ones. Such character of interlinear differences can be connected with properties of formation of the instrumental habit of deliverance from electropainful stimulus, because the presence of partition significantly hampered its fulfillment. The obtained results, compared with literature data, testify to the fact that differences of SHR and WKY rats in elaboration of conditioned reflexes are explained basically by the properties of their unconditioned activity and not of the associative processes.     

Analysis of the process of learning in the formation of the conditioned reflex of avoidance in rats

During acquisition of avoidance conditioned reflex (CR) in shuttle box by electric shock it is shown that the performance of that defence reaction is induced by the joint action of two factors: general arousal of animals and motivation. Motor activity of rats in an "open field", the number of short-latency (2s) and intersignal responses during formation of the avoidance CR are in index of the general arousal of rats. An artificial increase in the general arousal of animals by caffeine induces acceleration of CR performance. A constant level of the general arousal of rats is one of the reasons that oxytocin does not influence the rate and dynamics of the avoidance CR performance in rats.     

New data on the correlation of the cardiac and motor components of the instrumental conditioned defensive reflex in dogs

Correlation of heart rate (HR) and conditioned motor reaction (CMR) was studied in dogs with conditioned avoidance reflex by the V. P. Petropavlovski? method. An increase of HR was shown in response to presentation of conditioned sound stimulus reaching maximum directly before CMR beginning. Immediately after the beginning of CMR and further against the background of continuous keeping of the paw in the safety zone, CMR greatly decreases. The CMR changes testify to a heavy weakening of classical conditioned reflex of fear as a result of kinesthetic afferentation signalling about successful keeping of the paw in the safety zone.     

Neurophysiologic analysis of the critical period of delay of a reinforcing stimulus in the dog

At interval of less than 100 ms between indifferent sound and unconditioned electrocutaneous stimulation, classical defensive conditioned reflex is not elaborated in dogs, in full correspondence with literature data. But intracortical temporary connection is established; this fact is shown by electrographic phenomena, the most specific and demonstrative among them is "conditioned evoked potential". The absence of behavioural (peripheral) and presence of electrographic (central) manifestations allow to assume that for the formation of the conditioned reflex of full value the involvement is necessary of additional activational (motivational) mechanisms, connected with reticular and (or) limbic subcortical structures which do not react to the conditioned stimulus at time deficit in conditions of microdelay.     

Effect of a cyclic enkephalin analog on the protein content in the hippocampal neurons of rats during the acquisition of a 2-way avoidance conditioned reflex

The protein content has been determined by means of cytointerferometry in neurons of fields CA-1 and CA-3 of the dorsal hippocampus in rats, which were trained in a conditioned reflex of two-way avoidance (CRTA) with the action of subcutaneously injected enkephalin cyclic analogue (ECA) in a dose 10 mkg. It has been found that after ECA injection the protein content in the neuronal nuclei of the hippocampal CA-3 field reduces. The acceleration of the CRTA elaboration occurring during the action of ECA is accompanied by a drastic increase of the protein content in the neuronal nuclei of the CA-3 field. The ECA administration to the rats of the active control groups to which were presented the same number of unpaired conditioned and unconditioned stimuli as during the CRTA elaboration also enhances the protein content in the neurons of the CA-3 field. The rats of all investigated groups in the neurons of the CA-1 field display no such significant shifts. The conclusion has been drawn that ECA produces a regulating influence on protein metabolism in hippocampal neurons depending on their functional state.     

Reversal of signal significance of stimuli in the avoidance reflex]

The course of reversal learning in go -- no go avoidance reflex differentiation in both cats and dogs was analysed in terms of interrelations between drive and instrumental reflex activity. When signalling properties of the conditioned stimuli were reversed, marked changes in the drive state of experimental animals occurred. The increase of the fear drive influenced both the transfer of the instrumental response to the new positive conditioned stimulus and the extinction of the response to the previously positive stimulus. The quality of the conditioned stimuli and their reflexogenic strength exerted clear effects on the fear drive and on the course of reversal learning. Prefrontal lesions affected the drive state and the conditioned reflex activity of the animals during the reversal learning.     

Electroencephalographic studies on classically conditioned defensive reflex and avoidance lever-pressing in the dog (author's transl)]

Six dogs with implanted cortical and subcortical electrodes were trained to press a lever to avoid electroshock to a hind leg. Intracerebral stimulation at low frequency was delivered as an "indifferent" or a "CD" tracer. Changes of EEG responses to the tracers prior to the voluntary lever-pressing or the conditioned avoidance lever-pressing were prior to the voluntary lever-pressing or the conditioned avoidance lever-pressing were examined by continuous frequency analysis. (1) Evoked potentials to the tracer stimulation were changed just before the conditioned defensive reflex, the voluntary lever-pressing and the conditioned avoidance lever-pressing, regardless of the site of the tracer stimulation. (2) The cortical and subcortical structures (Hippo, RF) seemed to be involved in the neural circuit responsible for the avoidance lever-pressing, whereas the sensorimotor cortex may be essential in the circuit for the alimentary lever-pressing. (3) The avoidance lever-pressing and the EEG response to the "CS" tracer were influenced by the internal inhibition (experimental extinction, inhibitory mechanism was discussed.     

慢性动脉血压监测模型在惊恐条件反射中的应用

目的：探索一种新的、可靠的模型,用于惊恐条件反射的相关研究。方法：通过使用条件刺激(声音)和非条件刺激(足部电击)相结合的方法,可使动物对条件刺激产生惊恐反应。同时对动脉血压进行长期监测并测定利多卡因阻断杏仁基底外侧核群前后的血压变化。结果：该惊恐条件反射建立后(需经4d训练),单独给予动物条件刺激即可引起血压明显升高。我们将它作为条件反射已形成的标志。此时,用利多卡因阻断杏仁基底外侧核群的作用,单独给予动物条件刺激不再引起血压明显升高。结论：慢性动脉血压监测模型在惊恐条件反射的研究中是一种可靠的动物模型。     

Conditioned reflex transformation of unconditioned flexion of the limbs of the dog into extension

In response to electro-skin stimulation of the left forelimb eliciting its flexion,--an escape instrumental reflex was elaborated in five dogs in the form of extension of the stimulated limb (pressure on the support), i.e. a reaction antagonistic to the inborn one. The reaction was elaborated due to conditioned transformation of the unconditioned flexion: the flexion became gradually inhibited and the new form of reaction, previously not inherent in the animal increased and became stable. Such transformation of one reaction into another is connected with the reorganization of inborn coordinations.     

Fromation of forward and reverse connections during elaboration of a classical and instrumental acid-defense conditioned reflex

During elaboration of a classical acid defensive conditioned reflex to passive lifting of a foreleg in dogs, the reinforcing stimulus--acid elicited an extension of the leg via backward connection. At the initial stage of elaboration of an instrumental avoidance reflex, the reinforcing stimulus called forth an extension of the leg, whereas at the stage of a stable reflex it produced a flexion.     

The vegetative component of a conditioned reflex]

Defensive and alimentary conditioned reflexes were studied on normal cats and cats with neural isolation of the neocortex. The cardiac component of the conditioned reflexes is elaborated in decorticated animals at a similar rate and is as steady as in normal cats. Motor conditioned reactions in decorticated cats are difficult to elaborate. Both in normal and decorticated cats unconditioned pain stimulation evokes tachycardia, while a conditioned signal, paired with this unconditioned stimulus, produces bradicardia. Ban assumption has been made that the primary conditioned reaction consists in the appearance of a certain emotional state which changes the cardiac rhythm in a typical way.     

The effects of neuroleptics and nialamide on defensive conditoned reflex in rats.

Experiments were carried out on male Wistar rats after development of defensive conditioned relex during 6 weeks of training. In one series of experiments chlorpromazine, haloperidol, pimozide or fluspirilene were used in doses of 0.05, 0.5 and 5.0 mg/kg intraperitoneally. In another series of experiments nialamide was given intraperitoneally in a dose of 140 mg/kg 16--18 hours before administration of one of these neuroleptics. A delay in the time of appearance of the defensive conditioned refex was observed after administration of neuroleptics in all animals. In some rats neuroleptics caused complete disappearance of the conditioned refex as well as the defensive unconditioned refex. Previous inhibition of monoamine oxidase activity obtained with nialamide increased evidently the inhibitory effect of the studied neuroleptics on the appearance of defensive conditioned reflex.     

Integration of conditioned reflex systems in intact and callosotomized dogs

Characteristics of integrative activity were studied by Kupalov's method of situational conditioned reflexes in 2 groups of dogs with complete section of the callosal body and in group of intact animals. The dogs of the first group were callosotomized before the formation of the conditioned reflex systems, the dogs of the second group--after their stabilization. The level of the reflex systems integration in the first group was considerably lower than in the second one. This testifies to a special role of the callosal body in the initial period of formation of complex conditioned systems. The callosotomized dogs developed inertia of nervous processes which was manifested in slowing down of formation and of adaptive realization of reactions during integration of various reflex systems. It was shown that the integrative activity is provided for by the interaction of cerebral hemispheres at different structural levels.     

Sensitization and habituation of command neurons during a defensive reflex in grape snails

All investigated neurones were classified into functional groups depending on their participation in unconditioned avoidance reflex of pneumostome closure. Habituation was produced by tactile stimuli applied with a frequency of 0.1 c/s. Spike responses of neurons participating in processing sensory information habituated gradually, while reactions of command neurones of avoidance behaviour became sensitized to the second or third stimulus of the series. Behavioral reaction was sensitized in parallel with command neurones in spite of habituation in other types of nerve cells. A conclusion is drawn that behavioral habituation is due to waning of responses in all the participating neurones, but the independnet process of sensitization is due to sensitization of command neurones. Probable mechanisms of neuronal sensitization are discussed.     

Conditioning of active type avoidance in the rat : effect of the interval between conditioned stimulus and unconditioned stimulus

Lengthening the time interval between the conditioned stimulus and the unconditioned stimulus increases the number of active avoidance conditioned responses in subjects that have been trained to a stable level of performance in many previous conditioning sessions. In the present research, rats chosen from a population specially selected for low rates of avoidance conditioning have been used. In addition to this characteristic, subjects were chosen for the exhibition of an apparent absence of retention from one day to another. The dependency of the number of conditioned responses on the time interval between conditioned stimulus and unconditioned stimulus may lead to wrong evaluation of the subjects' conditioning level. In fact, the level of conditioning may be attributed to either learning or memory processes when in many cases it is determined only by the latency time of the conditioned response. The conditioned response has no possibility of manifesting itself when its latency time exceeds in length the time interval between conditioned stimulus and unconditioned stimulus.