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[The effects of acute administration of thyrotropin-releasing hormone on conditioned active avoidance learning and passive avoidance learning in rats (author's transl)].

The effects of acute administration of thyrotropin-releasing hormone (TRH) on the fear motivated learning of male Wistar rats were studied using a shuttle box. Two kinds of experiments - active avoidance learning (shuttle avoidance learning) and passive avoidance learning were performed. TRH (500 microgram/kg) was injected subcutaneously 40 to 50 minutes before the test trials. 1. In shuttle avoidance learning, TRH facilitated the acquisition after 8 sessions-pretraining and retarded the extinction after 8 approximately 12 sessions-pretrainings compared with saline. In passive avoidance learning, however, the reverse results were obtained: TRH retarded the acquisition and facilitated the extinction. 2. In shuttle avoidance learning, the acquisition facilitating effect of TRH was seen only in poor performer rats (poor performer was defined as less than 37 median score of conditioned avoidance responses in 8 sessions-pretraining), but not in good performer rats (more than 37 conditioned avoidance responses). 3. In shuttle avoidance learning, the acquisition facilitating effect of TRH was not seen in poor performer rats after 15 sessions-pretrainings, and the extinction retarding effect of TRH was not seen in the rats after 28 sessions-pretrainings. 4. From the above results it can be concluded that TRH possesses a fear reducing effect, and the behavioral changes brought about by TRH are seen most obviously in the rats which are in highly fearful conditions.

Animals↗

Forebrain serotonin and avoidance learning: behavioural and biochemical studies on the acute effect of p-chloroamphetamine on one-way active avoidance learning in the male rat.

The acute effects of p-chloroamphetamine (PCA) on one-way active avoidance learning and on central monoamine concentrations were examined in the male rat. The 5-HT specificity of the acute behavioural effect of PCA was examined in several experiments. PCA (0.08-5 mg/kg IP) injected 30-60 min before testing produced a dose-related impairment of both avoidance acquisition and retention. Pretreatment with the selective serotonin (5-HT) uptake inhibitors fluoxetine and zimelidine, but not the noradrenaline (NA) uptake inhibitor desipramine, resulted in a blockade of the avoidance deficit. Degeneration of brain 5-HT neurons by a high neurotoxic dose of PCA (2 x 10 mg/kg IP) 7 days prior to the administration of PCA also blocked the avoidance deficit. There was also a complete blockade of the PCA-induced avoidance deficit by pretreatment with metergoline, a central 5-HT receptor blocking agent. A 2.,5 mg/kg dose of PCA examined 60 min after injection produced regional changes in the 5-HT-levels preferentially in the forebrain region with significant reductions in the cerebral cortex, hippocampus and striatum while marginal effects were observed in the hypothalamus, midbrain and spinal cord. PCA failed to reduce dopamine and noradrenaline concentrations in the time- and dose-range of the avoidance deficit. Thus, the avoidance learning impairment appears to be specifically related to the acute release of endogenous 5-HT from presynaptic nerve endings possibly in the forebrain resulting in stimulation of postsynaptic 5-HT receptors. These findings indicate that 5-HT neurons in the forebrain play a role in active avoidance learning possibly by an involvement in memorial and/or retrieval processes.

Amphetamines↗

Basolateral amygdaloid multi-unit neuronal correlates of discriminative avoidance learning in rabbits.

Basolateral (BL) amygdaloid multi-unit activity was recorded as male albino rabbits learned to avoid a foot-shock unconditioned stimulus (US) by stepping in an activity wheel to an acoustic (pure tone) warning stimulus (CS+). A second tone (CS-) of different auditory frequency than the CS+ was presented in an irregular order on half of the conditioning trials but was never followed by the US. BL amygdaloid neurons developed, in the first session of conditioning, enhanced CS-elicited discharges relative to discharges recorded during pretraining with tones and noncontingent US presentations (excitatory plasticity), and greater discharges to the CS+ than to the CS- (discriminative plasticity). The discriminative plasticity attained maximal magnitude as the rabbits reached the asymptote of behavioral discrimination, and persisted during post-asymptotic training. Peak excitatory plasticity occurred in the session of the first significant behavioral discrimination and declined during the asymptotic and post-asymptotic stages of training. Similar patterns of excitatory and discriminative plasticity in structures directly interconnected with the BL nucleus (anterior cingulate cortex; medial dorsal thalamic nucleus) and effects of lesions suggest that the neurons in these areas participate in a circuit involved in mediation of avoidance learning.

Amygdala↗

Does the rat with hereditary hypothalamic diabetes insipidus have impaired avoidance learning and/or performance?

Avoidance learning and extinction of rats with hereditary hypothalamic diabetes insipidus (Brattleboro strain) were studied in 2 experiments that differed only in shock intensity. In both experiments rats homozygous for diabetes insipidus were more deficient in both escape and avoidance responding than were their heterozygous or normal controls. Although the hterozygous animals showed improved escape performance at the higher shock intensity, their avoidance behavior was not improved. The superiority of normal and heterozygous animals in extinction performance, relative to the homozygous animals, was eliminated or reversed when the differences in terminal acquisition performance were taken into account by analyses of covariance. Deficiency of ADH, therefore, may not result in faster extinction of avoidance behavior.

Animals↗

Involvement of hippocampal PKCbetaI isoform in the early phase of memory formation of an inhibitory avoidance learning.

Several evidences demonstrate that protein kinase C (PKC) is involved in hippocampal long-term potentiation (LTP) and in different forms of learning, including inhibitory avoidance training in rats. Here, we evaluated the levels of conventional PKC isozymes (alpha, betaI, betaII, gamma) in synaptic plasma membrane (SPM) fractions isolated from hippocampus of rats subjected to a one-trial inhibitory avoidance paradigm. At 0, 30 and 120 min after training, there was a significant increase in the total amount of PKCbetaI. Densitometric analysis of the immunoblots showed an increase of 142+/-11% at 0 min, 193+/-16% at 30 min and 156+/-6% at 120 min after training relative to shocked control values. No changes were found in PKCbetaI levels in SPM fractions of the shocked animals relative to naive control values. No training-specific increments in the levels of PKCalpha, betaII and gamma were observed at any time point tested. However, an increase in PKCgamma levels was found in trained and shocked animals sacrificed 120 min after each experimental procedure. In addition, bilateral microinjections of a fairly selective inhibitor of PKCbetaI isozyme into the CA1 of the dorsal hippocampus produced amnesia when given 10 min before training, or 50, 110, but not 170 min, after training. Thus, the present findings demonstrate the participation of PKCbetaI in the early synaptic events responsible for the acquisition and consolidation of an inhibitory avoidance learning, and suggest a putative role of this presynaptic isozyme on the enhanced PKC-dependent B-50/GAP-43 phosphorylation previously detected by us during this associative learning.

Animals↗

A systematic review of human avoidance learning: Cognition, computation, and methods.

Avoidance behaviour is fundamental for survival but can become maladaptive in clinical conditions. A large body of literature has accumulated on the dynamics of human avoidance learning. However, current theories and overviews do not provide an exhaustive account of this evidence. In this systematic review, we identify N = 116 studies on human avoidance learning. We analyse these studies with the goal of distilling robust empirical phenomena as a basis for theory-building, and examine their diagnostic value in differentiating between competing theories. We find that the evidence is difficult to reconcile with foundational two-factor and classical safety-signal accounts, and most strongly supports expectancy- and inference-based views, in which avoidance responses are selected with respect to represented consequences. At the same time, no current framework provides a complete account of the evidence: several findings point to an additional role for operant valuation, Pavlovian influences, and contextual or latent-state control over the expression of avoidance. Methodologically, we observe that the problem setting in the most common experimental paradigms is radically simpler than real-world avoidance and therefore unlikely to expose the limits of inferential or reflective mechanisms. Consequently, we argue that paradigms with greater computational demands and more realistic action affordances are required to identify the mechanisms underlying avoidance learning. Collectively, these insights provide a foundation for theoretical refinement, computational modelling, and methodological innovation, with implications for advancing interventions targeting maladaptive avoidance.

Humans↗

Reaction to punishment, reflectivity, and passive avoidance learning in extraverts.

Passive avoidance learning occupies a central role in accounts of disinhibited behavior, ranging from psychopaths' persistent criminality (Hare 1970) to extraverts' gregariousness (Gray, 1972). To explore the mechanism underlying passive avoidance deficits, we assessed the relation of extraversion, neuroticism, and response latency after punishment to passive avoidance learning by using two successive go/no go discrimination tasks. The tasks were designed to examine two aspects of subjects' reactions to punishment: response speed on trials immediately following punishment (Experiment 1) and time to terminate punishment feedback between successive trials (i.e., reflectivity; Experiment 2). Consistent with previous findings, the results of Experiment 1 showed that extraverts commit more passive avoidance errors than introverts do (Newman, Widom, & Nathan, 1985) and fail to pause following punished errors (Nichols & Newman, 1986). In Experiment 2, only neurotic extraverts displayed this pattern of performance differences. In both experiments, longer pausing following punishment predicted better learning from punishment for both introverts and extraverts. These results suggest that, in the presence of salient cues for reward, extraverts' characteristic reaction to punishment interferes with processing punished errors and may contribute to their more general propensity for impulsive, nonreflective action.

Avoidance Learning↗

Sensory responsiveness and avoidance learning in rats.

Analysis of sensory responsiveness and avoidance learning was carried out in three experiments using five rat strains. There were significant differences among the strains in response to electric footshock. Also the strain-specific shock intensity as unconditioned stimulus (US) elicited significantly higher rates of avoidance learning as compared with the rates of avoidance learning under an equal but average level of shock intensity as US. In general, discrete auditory and visual sensory modes as conditioned stimuli (CS) produced almost the same rate of avoidance learning. The proportion of variation in avoidance learning attributable to strains was significant under all six experimental conditions except no-discrete CS and strain-specific US condition.

Acoustic Stimulation↗

Effects of antimuscarinic cholinergic drugs injected systemically or into the hippocampo-entorhinal area upon passive avoidance learning in young rats.

Passive avoidance learning was significantly impaired by atropine (5 mg/kg, IP) or scopolamine (0.5 mg/kg), but not by methyl-atropine (5 mg/kg) or methyl-scopolamine (0.5 mg/kg), from postnatal day 15 on. In contrast, an improvement was observed, not significant at 11 days and significant at 13 days, probably due to nonspecific effects. Retention of the response increased from 6 h at 13 days, to 24 h at 17 days. In treated rats, retention was abolished at 13 and 15 days, and impaired at 17 and 20 days. Acquisition of the response was also significantly impaired by bilateral injections of atropine (1, 5, and 20 micrograms) into the posteroventral hippocampo-entorhinal (VHE) area, from day 15 on. Concomitantly, extinction was accelerated. At 14 days, atropine had no influence. At 13 days, a facilitatory action was observed, with better acquisition and greater resistance to extinction, possibly linked to affective changes. The results confirm that central muscarinic cholinergic mechanisms are involved in passive avoidance learning from postnatal day 15 on, and demonstrate that some pathways of this system are located in the VHE area, become efficient at 15 days, and improve markedly between 17 and 18 days.

Age Factors↗

Chemical sympathectomy and two-way escape and avoidance learning in the rat.

Six experiments are reported on the effects of 2,4,5-trihydroxyphenylethyl-amine (6-hydroxydopamine) on two-way escape and avoidance learning. Rats were tested on either escape or avoidance learning at 80 days of age after chemical sympathectomy at birth or 40 or 80 days of age. Neonatal and chronic sympathectomy (at 40 days), but not acute sympathectomy (at 80 days), resulted in depressed escape learning. Avoidance learning was affected by neonatal sympathectomy and partially by acute sympathectomy. The results have implications for the role of the autonomic nervous system in escape-avoidance learning.

Age Factors↗

Lesions in the central nucleus of the amygdala: discriminative avoidance learning, discriminative approach learning, and cingulothalamic training-induced neuronal activity.

The amygdala is critically involved in discriminative avoidance learning. Large lesions of the amygdala block discriminative avoidance learning and abolish cingulothalamic training-induced neuronal activity. These results indicated that amygdalar processing is critical for cingulothalamic plasticity. The larger lesions did not allow differentiation of the specific functioning of various amygdalar nuclei. Anatomical analysis showed that damage in the central (CE) nucleus of the amygdala was correlated with the severity of the behavioral deficit. The present study was carried out to determine whether smaller lesions, centered in the CE nucleus, would impair discriminative avoidance learning and block cingulothalamic plasticity. In addition, the possible role of the CE nucleus in appetitively motivated discriminative approach learning was examined for the first time. New Zealand White rabbits with CE nuclear lesions were first trained in the discriminative approach task. After attaining asymptotic performance, discriminative avoidance training sessions were alternated with continuing approach training sessions, one session each day. The rabbits with lesions were severely impaired in avoidance learning but showed no impairment of approach learning. Surprisingly, the attenuating effects of the lesions on cingulothalamic training-induced neuronal activity were more prevalent during approach learning than during avoidance learning. These results indicated that avoidance learning can be impaired by lesions centered in the CE nucleus that leave cingulothalamic plasticity largely intact and that the CE nucleus is involved in extra-cingulothalamic learning processes.

Amygdala↗

Development of amygdaloid cholinergic mediation of passive avoidance learning in the rat. I. Muscarinic mechanisms.

Passive avoidance learning was studied in young rats 13-30 days of age following bilateral injections of saline or antimuscarinic and/or muscarinic agents into three amygdaloid nuclei--lateral (L), basolateral (BL), and cortical (CO). While acquisition was not influenced by saline injections into various other cerebral structures, it was significantly altered by similar injections into these amygdaloid nuclei, especially by those into the BL nucleus, suggesting that this nucleus is particularly involved in passive avoidance learning. Atropine induced significant deficits from as early as 13 days on. These deficits increased and were of similar strength after injections into any of the three studied nuclei until day 16; after that age, they diminished slightly following CO and L nuclei administration, while remaining substantial after BL nucleus injections at all ages, even at 30 days. No facilitatory effects could be elicited by arecoline injected alone, while arecoline could antagonize the disturbing effect of atropine, when given in combination, from day 13 on. These results suggest a muscarinic cholinergic mediation of passive avoidance learning through the synaptic elements located in the basal lateral part of the amygdala in the young rat.

Acetylcholine↗

Food avoidance learning in squirrel monkeys and common marmosets.

Using a conditioned food avoidance learning paradigm, six squirrel monkeys (Saimiri sciureus) and six common marmosets (Callithrix jacchus) were tested for their ability to (1) reliably form associations between visual or olfactory cues of a potential food and its palatability and (2) remember such associations over prolonged periods of time. We found (1) that at the group level both species showed one-trial learning with the visual cues color and shape, whereas only the marmosets were able to do so with the olfactory cue, (2) that all individuals from both species learned to reliably avoid the unpalatable food items within 10 trials, (3) a tendency in both species for quicker acquisition of the association with the visual cues compared with the olfactory cue, (4) a tendency for quicker acquisition and higher reliability of the aversion by the marmosets compared with the squirrel monkeys, and (5) that all individuals from both species were able to reliably remember the significance of the visual cues, color and shape, even after 4 months, whereas only the marmosets showed retention of the significance of the olfactory cues for up to 4 weeks. Furthermore, the results suggest that in both species tested, illness is not a necessary prerequisite for food avoidance learning but that the presumably innate rejection responses toward highly concentrated but nontoxic bitter and sour tastants are sufficient to induce robust learning and retention.

Animals↗