Reproduction of passive avoidance reactions after neurotensin microinjection into nucleus accumbens of rat brain against the background of reserpine action

The purpose of the study was to reveal the features of the influence of neurotensin injected into the nucleus accumbens on behaviour of rats after systemic administration of reserpine in the dose of 2 mg/kg. Reprodution of passive avoidance conditioned reactions, painful stimulation aftereffects on locomotor activity in the "open field", and behavior in the elevated plus-maze were studied. It was shown that reserpine administration impaired the reproduction of passive avoidance reactions and weakened the oppressing aftereffect of painful stimulation, which can be due to a decrease in anxiety in rats. Neurotensin prevented disorders in the defensive behavior evoked by reserpine and intensified the state of anxiety in the elevated plus-maze. The positive influence ofneurotensin on the reproduction of passive avoidance can be associated with the recovery of the anxiogenic effect of painful stimulation destroyed by reserpine. Thus, neurotensin injected into the nucleus accumbens could normalize the balance of brain monoaminergic systems.     

Levels of arginine-vasopressin in cerebrospinal fluid during passive avoidance behavior in rats

The concentration of immunoreactive arginine-vasopressin (IR-AVP) was measured in the cerebrospinal fluid (CSF) during acquisition and retention of passive avoidance behavior. IR-AVP level in CSF of male Wistar rats immediately after the learning trial was increased; the rate of which was related to the intensity of the electric footshock during the learning trial and the avoidance latency as measured 1 day after the learning trial. Immediately after the 24 h retention test IR-AVP levels were significantly increased in rats subjected to the low (0.25 mA) shock intensity during the learning trial, but IR-AVP levels of rats exposed to the high shock (1.0 mA) were under the limit of detection. If the retention test was postponed till 5 days after the learning trial, the increase of IR-AVP level in the CSF was related to avoidance latencies which reflect the intensity of aversive stimulation (electric footshock). The results suggest an association between central AVP release and passive avoidance behavior and may be indicative of the role of this peptide in neuronal mechanisms underlying learning and memory processes.     

Effect of alpha-tryptophan on conditioning and behavior in rats with experimental pathology of the thyroid gland

Effects of L-tryptophan on learning and behavior were studied in male rats with a deficit or excess of thyroid hormones. Learning was assessed in active avoidance paradigm, and behavior was estimated in the "open-field" test. It was found that L-tryptophan restored the capability of thyreoidectomized rats for acquisition and reproduction of the active avoidance reaction and increased the exploratory behavior of these rats in the open-field. In triiodothyronine treated rats, L-tryptophan eliminated a light stimulatory effects of thyroid hormones on the processes of formations and retention of the active avoidance reaction, increased the exploratory activity, but decreased grooming in the open-field.     

Effects of D2 receptor agonist and antagonist on behavior of intact and ovariectomized rats

The involvement of D2 dopaminergic receptors in behavioral responses during ovary cycle was assessed in adult intact female rats and ovariectomized (OVX) female rats. Quinperole (0.1 mg/kg), D2 receptor agonist and sulpiride (10.0 mg/kg), D2 receptor antagonist were injected chronically to adult intact and ovariectomized (OVX) female rats either separately or in combination with 17beta-estradiol (0.5 microg) within 14 days. Behavior of these animals was assessed in the "open field" test, whereas passive avoidance performance served as a model of learning. In intact rats, the passive avoidance performance was observed only in metestrous and diestrous. Chronic quinperole administration to intact females resulted in the appearance of the passive avoidance performance in proestrous and estrous, as distinct from the control animals. The passive avoidance performance was not reproduced in OVX rats. Quinperole per se or in combination with 17beta-estradiol completely restored the passive avoidance performance in OVX rats. Moreover, quinperole or sulpiride administration to OVX rats increased horizontal locomotor activity, exploratory behavior, and grooming behavior.     

The effect of administering corticoliberin into the striatum on the open-field and shuttle-box behaviors of KHA and KLA strain rats]

The effects of corticotropin-releasing hormone (CRH) injected into the dorsal neostriatum on the open-field and shuttle-box behavior were studied in rats with high (Koltushi high avoidance, KHA) and low (Koltushi low avoidance, KLA) capability for avoidance learning. The effects of this hormone on the behavior of these rat strains were different. In KLA rats with passive strategy of behavior the CRH injection led to a rapid locomotor activation in the open field, while the rats with active behavioral strategy (KHA) reacted to the injection by a significant decrease in locomotion and change for the passive mode of behavior. The same CRH effects on locomotion were obtained in the shuttle-box experiments. Moreover, in the KLA rats the neurohormone injection resulted in an improvement of avoidance learning in contrast to the KHA rats, in which CRH substantially impaired avoidance learning. The obtained evidence is discussed in terms of the important role of striatal CRH in the choice of behavioral strategy in stress.     

Changes in serum corticosterone and testosterone during induced maternal behavior in rats

Serum corticosterone (Cpd B) and testosterone (T) concentrations were studied during the avoidance phase of artificially induced parental behavior in male rats. Adult rats were exposed to the presence of standard size foster pups for 60 min daily. On day 1 the avoidance behavior characterized by typical burying reaction was accompanied by an elevation of Cpd B and T. The behavioral responses and hormonal changes diminished during the days of repeated exposure. It was found that neither pup-killing nor spontaneous retrieval were dependent on circulating hormones in the male rat. Subcutaneous injection of ACTH 4-10 inhibited extinction of the avoidance and the humoral responses in both female and male animals. Oxytocin failed to exert any influence on the behavioral and hormonal components of the aversive reaction.     

Spontaneous and conditioned behavior of Wistar and Long Evans rats

Spontaneous behavior (locomotion, feeding, drinking, and exploration in a two box apparatus) as well as conditioned behavior (passive and active avoidance responding, and freezing in the light-dark box apparatus) were studied in naive male Wistar and Long Evans rats. Concerning spontaneous behavior, Long Evans rats were more active during both light and dark periods, and showed better exploratory performance than Wistar rats. Concerning conditioned behavior, Long Evans rats acquired and retained better active and passive avoidance responses, and exhibited longer initial freezing than Wistar rats in the range of 0.6-1.4 mA footshocks. The results better define the important behavioral differences existing between the two strains, Long Evans rats showing consistently a higher level of alertness and a better conditioned performance.     

Typological features of behavior and memory in Norway rats selected for absence of aggression toward a man

Features of behavior and retrieval of passive conditioned avoidance on a new and forgotten stimuli were compared in Wistar rats and Norway rats bred for the absence of aggression toward a man. As distinct from white rats, grey rats were characterized by low anxiety and high locomotor exploratory activity in the elevated plus maze and dark-light chamber. Norway rats demonstrated better avoidance performance with active defensive behavioral strategy than Wistar rats. Latent inhibition during conditioning with a previously forgotten situational stimulus was the same in both rat strains. The results are discussed in terms of the use of grey rats as a model for an in-depth analysis of the mechanisms of memory optimization.     

Tolerance to the anti-avoidance properties of cholecystokinin-octapeptide

Previous investigations have suggested a neuroleptic-like action of cholecystokinin-octapeptide (CCK8) on conditioned-avoidance behavior. This study was initiated to test tolerance to this effect. Rats were trained to avoid electric shock in a shuttle box under a free-operant (Sidman) avoidance paradigm. Each shuttle response postponed a 0.2 sec, 1 mA shock for 20 sec. If the rat failed to respond, shock was delivered every 5 sec until a response occurred. After avoidance training, half of the rats received two daily injections of CCK8 (0.320 mg/kg, IP) and half received saline for 7 days. Rats were then tested on the Sidman avoidance 1 min after receiving CCK8 (0.640 mg/kg, IP) or saline. CCK8 depressed avoidance responding if rats received saline for 7 days prior to the test. Rats pretreated with CCK8 for 7 days were not significantly affected by CCK8 during the avoidance test. Thus, repeated injections of CCK8 result in tolerance to its anti-avoidance properties.     

Effects of oxytocin and vasopressin on retrieval of passive avoidance response in melatonin-treated and/or pinealectomized male rats

The role of the pineal gland and its hormone-melatonin-as to the impact of vasopressin (VP) and/or oxytocin (OT) on the regulation of behavior was studied, the passive avoidance task being chosen as an experimental model. The results showed that VP facilitated the avoidance latency during the first retention trial; after pinealectomy, however, VP was ineffective in this regard. Intraperitoneal application of OT was ineffective in modifying the passive avoidance latency when compared with respective saline-treated animals. Melatonin alone, when injected to shamoperated animals 30 min before behavioral experiment, did not affect the passive avoidance response in SA- or OT-treated rats, but blocked the VP-induced lengthening of the passive avoidance latency in the first retention trial. In pinealectomized and OT-treated animals the passive avoidance latency during the second retention trial was severely diminished by melatonin when compared to respective control. We conclude that: a) VP needs a regulated pineal function for developing short-term effects on the passive avoidance response and b) the effect of OT on the avoidance latency in pinealectomized rats develops after melatonin treatment as a long-term effect.     

Developmental caspase-3 activation in the rat hippocampus is involved in the maturation of instrumental behavior

Previously the developmental switch to caspase-3 activation in the rat hippocampus has been shown during the third week of life. The goal of this study was to explore effects of caspase-3 inhibition during this period on learning in a two-way avoidance paradigm. On postnatal day 18, the pups were intracerebroventricularly administered with caspase-3 inhibitor Z-DEVD-FMK. Control groups were injected with either the control peptide Z-FA-FMK or saline. Caspase-3 inhibition, naturally activated in this critical period, was found to disturb the maturation of instrumental behavior. In particular, the young adult rats of Z-DEVD-FMK group displayed less effective elaboration of escape and active avoidance reactions in two-way avoidance paradigm, accompanied with a decrease in inter-trial crossings. However, associative components of the learning did not change after caspase-3 inhibition. Conditioned emotional behavior was, in general, similar in all groups, and the number of responses related to conditioned stimulus exploration did not differ in Z-DEVD-FMK and Z-FA-FMK groups. In spite of the deficit in active avoidance conditioning in Z-DEVD-FMK group, a significant increase in incomplete or preparatory reactions to conditioned stimulus was demonstrated suggesting that the association between predictive conditioned stimulus and possibility of crossing can be elaborated. The change of exploratory behavior is unlikely to be specific for caspase-3 inhibition, being similar in Z-DEVD-FMK and Z-FA-FMK groups.     

The ACTH-(4-9) analog ORG 2766 and desglycinamide9-(Arg8)-vasopressin reverse the retrograde amnesia induced by disrupting circadian rhythms in rats

Disrupting circadian organization by exposing rats to a shifted illumination schedule after training for passive avoidance and shuttle box avoidance behavior resulted in retrograde amnesia as evidenced by impaired performance during retention and extinction testing respectively. A single treatment with either the ACTH-(4-9) analog ORG 2766 or desglycinamide9-(Arg8)-vasopressin (DGAVP) 1 hour prior to the retention of passive avoidance or extinction of shuttle box avoidance behavior restored the behavioral impairment. It is suggested that these peptides may be useful to relieve memory deficits induced by disturbances in circadian organization.     

Telemetered heart rate responses of the rat during free and learned behavior

To assess the effect of recording on the heart rate and on the behavior of the free moving rat, the electrocardiogram was recorded with the aid of radiotelemetry or through wire leads attached to the animal in different behavioral situations. Adaptation of heart rate both within and across sessions in the home cage and in a novel environment (open-field) was observed in rats bearing a transmitter. No adaptation occurred in rats attached to wire leads. The pattern of heart rate changes appeared to be independent of the mode of recording during passive avoidance behavior and when the rats displayed various motor activities like walking, sniffing, rearing or grooming in the open-field. The heart rate of rats attached to wire leads, however, was always higher. These data indicate that radiotelemetry is preferable to the use of wire connections for recording cardiac activity during behavioral studies in the rat.     

Comparative study of the psychotropic activity of tuftsin and its analogs

Tuftsin and its Leu1 and D-Arg4 analogs displayed stimulating activity in experimental behavioral despair in mice. In rats with different types of emotional reactions and with destroyed catecholamine terminals (6-OHDA treatment), tuftsin increased exploratory activity, with fear manifestations being decreased and avoidance behavior improved. This was shown while testing the rats in the "open field" and according to the ability to accomplish an extrapolation task of avoiding critical stress-situation. Leu1-tuftsin increased the emotional stress and sharply hindered the avoidance reaction, while D-Arg4-tuftsin modulated the behavior of the animals with increased emotional reactivity and made the avoidance behavior prompter. Pentapeptide, an inhibitor of tuftsin stimulation of phagocytosis, had no significant effect on the behavior. Modifications in the structure of tuftsin resulted both in the changes in phagocytosis-stimulating activity and the appearance of other psychotropic effects.     

Effect of consumption of sucrose and saccharin on passive avoidance learning in female Wistar rats

Influence of consumption of 32% sucrose or 0.1% saccharin solutions on passive avoidance acquisition in female Wistar rats was studied at different stages of estrous cycle. Under conditions of weak electrical shock, rats of the control and saccharin groups showed no acquisition at any stage of estrous cycle. Under the same conditions females of the sucrose group acquired the avoidance behavior if trained on the first day of diestrous and metestrous but not proestrous and estrous. The stage of estrous cycle on the second day did not influence the latency during testing session.     

The role of corticotropin-releasing hormone in alteration of adaptive behavior of the active and passive rats after inescapable stress

Effects of corticotropin-releasing hormone (CRH) on the formation of post-stress psychopathology were studied using of two genetic strains KHA (Koltushi high Avoidance) and KLA (Koltushi low Avoidance) selected on high or low acquisition of active avoidance, respectively. These strains are characterized by higher (KHA) and lower (KLA) behavioral activity in open field and adopted, respectively, active and passive strategies in stressful conditions. A widely used experimental paradigm of learned helplessness where behavioral depression was produced by inescapable uncontrollable footshock has been applied in our study. KHA rats demonstrated psychopathology already 1st day following exsposure to the stress faktor, and the depression progressed by the 5th and 10th post-stress days. Intranasal application of CRH facilitated the development of depression in active rats. In KLA rats, which originally displayed low exploratory activity associated with high anxiety, the inescapable stress at first enhanced the exploratory behavior but 10 days later these rats displayed a progressive decline of exploration and locomotion. Initially, the application of CRH also enhanced the exploratory behavior in these rats, but to 10th post-stress day promoted development of depressive state. The results suggest that CRH in different ways affects the formation of depressive state in rats with different strategies of adaptive behavior.     

Effect of sexual steroids and androgen sterilization on avoidance and exploratory behaviour in the rat

The effect on avoidance and exploratory behavior of large doses of sexual steroids or of changes in ovarian steroid secretion induced by gonadotropin treatment or androgen sterilization was studied in female R-Amsterdam rats. Estrogen, progesterone, testosterone, androgen sterilization, and human chorionic gonadotropin (HCG) effects were tested and evaluated. Estrogen in castrated female rats delayed extinction of the conditioned avoidance response from Day 8 of extinction and increased intertrial activity during extinction. Estrogen treatment applied from extinction was ineffective. Progesterone treatment of castrated female rats applied from the first days of conditioning delayed extinction from Day 12. If the treatment was begun at extinction, this was delayed after Day 8. Intertrial activity was also higher between Day 8 and Day 15 of extinction. Testosterone treatment of castrated male rats increased intertrial activity during acquisition. In the animals treated from extinction, a delay was observed from Day 9, and intertrial activity was increased simultaneously. In androgen-sterilized female rats, extinction was facilitated. HCG treatment of intact female rats delayed the extinction. The steroids used failed to affect the exploratory activity of castrated rats, indicating that, under the conditions tested, general activity and exploratory activity are not motivated by the same mechanism.     

The characteristics of higher nervous activity and of the brain benzodiazepine system in rats subjected to ethanol exposure in the prenatal period

Exposure to ethanol during pregnancy results in the alternation of 3H-diazepam binding to synaptosomal neocortical membranes from the rat offspring. In male experimental rats, 14 days of age, binding level diminished to 11%. In two-month-old control rats Scatchard plot was biphasic. It has been shown that prenatal exposure to ethanol leads to changes in the nature of binding in two-month-age experimental animals, as compared with the control ones. 3H-diazepam binding changes went along with behavioural deviations. In experimental rats locomotor activity was increased in the "open field" test, passive avoidance conditioned reflex retention was decreased and elaboration parameters of active avoidance conditioned reflex were changed, as compared with the control ones. The data obtained show that higher integrative functions were disturbed by prenatal alcoholization. Correlations between benzodiazepine receptor state and behaviour were studied.     

The role of neurochemical mechanisms of the dorsal raphe nucleus in various models of anxiety states in rats

Dopamine and serotonin microinjection in the dorsal raphe nucleus of rats does not influence the alarm state in the test of "threatening situation" avoidance, but increases or weakens the state of alarm in the rest of "illuminated site" avoidance. Local injection of GABA in this midbrain formation weakens the alarm state in the test of "threatening situation" avoidance but is not effective in the test of "illuminated site" avoidance. Chemical stimulation of the raphe nucleus by glutaminic acid does not influence the two different experimentally modelled states of alarm, but modulates the mechanisms controlling the instinct of darkness preference by rats.     

Involvement of serotoninergic brain structures in the mechanisms of neurotensin effect on passive avoidance in rats

The purpose of the research was to reveal the features of neurotensin (administered in substantia nigra or dorsal raphe nucleus) effect on recall of passive avoidance reactions in rats. It was shown that the effect of neurotensin injected into the substantia nigra was characterized by a sharp reduction of passive avoidance reactions. On the contrary, injection of the substance in the dorsal raphe nucleus led to an intensification of these reactions and delay of their extinction. The effects of microinjections of serotonin 1A receptor agonist, 8-hydroxy-dipropylaminotetralin (8-OH-DPAT), into the mentioned brain structures was similar to that of neurotensin. Changes in the content of serotonin and its metabolite 5- hydroxyindoleacetic acid (5-HIAA) in the caudate nucleus corresponded to various behavioral effects. The conclusion was made that neurotensin effect on the passive avoidance behavior is related to regulation of emotional state of animals mediated by its action on the function of the serotoninergic brain structures.