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Apparatus exposure produces profound declines in conditioned nictitating-membrane responses to discrete conditioned stimuli by the rabbit (Oryctolagus cuniculus).

The present experiments demonstrated that in the rabbit (Oryctolagus cuniculus) nictitacing-membrane (NM) preparation, exposure to the experimental apparatus produces profound declines in conditioned responding to a discrete conditioned stimulus (CS; Experiments 1, 2A, and 3). Moreover, this decremental effect is at most attenuated in only a minor way when the unconditioned stimulus (US) is presented during exposure to the apparatus (Experiment 2B). Controls for retention loss (Experiments 1 and 3) and for handling and placement in a different context (Experiment 3) did not produce significant declines in responding. These findings challenge theories of extinction that rely primarily on context-US associations but are more consistent with theories that assume context-CS-US associations.

Animals↗

Effects of lesions of the bed nucleus of the stria terminalis, lateral hypothalamus, or insular cortex on conditioned taste aversion and conditioned odor aversion.

The effects of permanent forebrain lesions on conditioned taste aversions (CTAs) and conditioned odor aversions (COAs) were examined in 3 experiments. In Experiment 1, lesions of the bed nucleus of the stria terminalis had no influence on CTA or COA acquisition. Although lesions of the lateral hypothalamus induced severe hypodipsia in Experiment 2, they did not prevent the acquisition of CTAs or COAs. Finally, in Experiment 3, lesions of the insular cortex retarded CTA acquisition but had no influence on COA acquisition. The implications of these findings are discussed with regard to the forebrain influence on parabrachial nucleus function during CTA acquisition.

Analysis of Variance↗

Survival after reduced-intensity conditioning is not inferior to standard high-dose conditioning before allogeneic haematopoietic cell transplantation in acute leukaemias.

To assess the role of allogeneic stem cell transplantation (SCT) after reduced-intensity conditioning (RIC) in acute leukaemias, we retrospectively compared 25 patients with acute lymphoblastic leukaemia or acute myelogenous leukaemia after RIC to a historical group of 50 matched controls after high-dose conditioning. Engraftment, acute GvHD and severe infections were comparable in both groups. During the observation period, 1/25 patients (4%) after RIC and 14/50 (28%) after standard SCT died due to transplant-related causes; cumulative nonrelapse mortality (NRM) was 4% after RIC and 24% after standard SCT (P=0.029). In total, 15/25 patients (60%) relapsed after RIC and 20/50 (40%) after standard SCT; probability of disease-free survival (DFS) at 3 years was 43% after RIC and 49% after standard SCT (NS). Overall survival (OS) was 40% after RIC and 37% after standard SCT (NS). Stage of disease, cytogenetic risk profile, acute and chronic GvHD, chimerism status at day 90 and severe infections after transplantation were risk factors with significant impact on DFS and/or OS. In retrospective analysis, patients with acute leukaemias who receive RIC because of contraindications against standard SCT have a comparable outcome to standard SCT, but the higher relapse rate warrants further studies.

Acute Disease↗

Opiates and classical conditioning: selective abolition of conditioned responses by activation of opiate receptors within the central nervous system.

It has previously been shown that opiates produce selective abolition of aversively motivated classically conditioned responses in the rabbit. The experiments reported here show that these effects are mediated by specific activation of opiate receptors within the central nervous system in that this central activation is both necessary and sufficient to produce opiate-induced abolition of conditioned responding. Further characterization suggests that selective activation through opiate-mu-receptor interactions within the periaqueductal gray/periventricular region of the fourth ventricle may be critical in mediating this abolition.

Avoidance Learning↗

7-Nitroindazole blocks nicotine-induced conditioned place preference but not LiCl-induced conditioned place aversion.

We have shown previously that the neuronal nitric oxide synthase (nNOS) is involved in the rewarding effect of cocaine as determined by the conditioned place preference (CPP) paradigm. In the present study we investigated the effect of the nNOS inhibitor 7-nitroindazole (7-NI) on nicotine-induced CPP and LiCl-induced conditioned place aversion (CPA) in Swiss Webster mice. Mice treated with nicotine (0.5 mg/kg) or saline every other day for 8 days (four drug and four saline sessions) developed CPP that was completely blocked by pretreatment with 7-NI (25 mg/kg). Mice treated with LiCl (150 mg/kg) developed marked aversion to the LiCl-paired compartment. LiCl-induced CPA was not affected by the pretreatment with 7-NI. These findings suggest that nitric oxide (NO) plays a role in the acquisition of reward but not of aversion and that the blockade of nicotine-induced CPP is probably not due to impairment of learning and memory.

Animals↗

Apomorphine sensitization: evoking conditions, context dependence, effect persistence and conditioned nature.

When repeatedly administered a dose of apomorphine (Apo), pigeons, much like rodents, show behavioural sensitization. In birds this sensitization expresses itself as an increasing pecking response to the drug and is found to be partially dependent on the environmental context in which Apo takes effect. In the first experiment we examined what effect different inter-Apo administration intervals have on the development of Apo sensitization and found that, with some smaller variations, intervals between 3 hours and 5 days all yielded comparable courses of sensitization. In the second experiment we examined how long pigeons had to be exposed to the same distinct cage to reveal a maximal context-dependent sensitization. Pigeons were therefore repeatedly injected with Apo and consistently placed in an experimental cage for different lengths of time (5 to 60 min; the overall drug effect lasted for about 1 h) before being returned to their standard home cages. Subsequent tests in the experimental cage and a standard cage showed that 20-min post-injection exposures were sufficient to yield a maximal response in the experimental cage. After training with 20- and 60-min exposures, the pigeons pecked about three times more in the experimental cage than in the standard cage. This confirmed the marked context dependency of the sensitization effect. In the third experiment, groups of pigeons were injected repeatedly with Apo and directly afterwards placed either consistently into the same experimental cage or into different experimental cages. The same-cage group evidenced a significantly much stronger sensitization than the different-cage group. A cage-habituation group served as a control for the possibility that the weaker sensitization of the different-cage group might be due to a cage novelty effect. This cage-habituation group was run under the same conditions as the different-cage group but with additional exposures to the crucial cage while injected with saline. This extra treatment did not augment the pecking response to Apo in that cage. In the fourth experiment we examined how long the sensitization to Apo lasts and found that, even after 2 years of drug abstinence, it only waned to 50% of the original asymptotic response. The overall results support the hypothesis that a very major part of the sensitization to Apo in pigeons is due to a conditioning to the environmental context and to the drug state itself.

Animals↗

Body temperature as a conditional response measure for pavlovian fear conditioning.

On six days rats were exposed to each of two contexts. They received an electric shock in one context and nothing in the other. Rats were tested later in each environment without shock. The rats froze and defecated more often in the shock-paired environment; they also exhibited a significantly larger elevation in rectal temperature in that environment. The rats discriminated between each context, and we suggest that the elevation in temperature is the consequence of associative learning. Thus, body temperature can be used as a conditional response measure in Pavlovian fear conditioning experiments that use footshock as the unconditional stimulus.

Animals↗

Conditioned acceleration and conditioned suppression in pigeons.

Two experiments were performed to investigate the effects on pigeons' keypecking behavior of stimuli that signal different kinds of aversive events: time-out from positive reinforcement, electric shock, loud noise, and loud tone. Behavior maintained by a variable-interval schedule of reinforcement was suppressed by a stimulus before shock, was accelerated by a stimulus before time-out from positive reinforcement, and was unchanged by a stimulus before loud noise or a stimulus before loud tone. Conditioned acceleration with time-out from positive reinforcement and conditioned suppression with shock were obtained regardless of whether a response contingent or response-independent procedure was employed.

Animals↗

Pavlovian conditioning of the tickle response of human subjects: temporal and delay conditioning.

Previous studies of the human response to a tickle have demonstrated that subjects will respond to a gesture that signals the onset of a tickle in the same way as to a tickle. Researchers have described this anticipatory response as an "expectation." In the current study, we investigated, from the Pavlovian framework, the response to a verbal stimulus preceding the tickle stimulus. We exposed subjects to experimental phases which included the Neutral Stimulus Alone, 100% Pairing of the Neutral and Unconditioned Stimuli (tickle strokes to the foot), Random Presentation, Partial (75%) Reinforcement, and Temporal Conditioning. Pavlovian conditioning was observed in all phases, suggesting a parsimonious explanation for the expectation effect described by others.

Adult↗

[Electrographic correlates of "inner states" caused by positive conditioned stimuli in the course of instrumental conditioning in dogs].

Energy characteristics (power spectra) of short-term (less than 1 s) EEG-reactions were studied in dogs in the course of instrumental conditioning. These reactions were observed in different areas of the cortex during selective attention in response to positive conditioned stimuli. They immediately preceded strong blow with a paw on the pedal of feeding cup and taking the reward. The EEG power at these moments was 1.5-3 times higher than the baseline EEG power level in a prestimulus period. The high-frequency structure of corresponding EEG reactions comprised discrete individual spectral peaks both in traditional (1-30 Hz) and gamma (30-80 Hz) ranges and higher-frequency components (80-200 Hz) as well. In some cases, the higher-frequency components (80-200 Hz) were most pronounced.

Animals↗

[Electrographical correlates of adequate and erroneous responses caused by conditioned signals of different functional sign during instrumental conditioning in dogs].

Power spectral (in the broad frequency band of 1-225 Hz) of short-term (less than 1 s) EEG reactions were studied in dogs in the course of instrumental food conditioning. These reactions appeared in different cortical areas in response to differentiating signals under conditions of both adequate and erroneous responses. The EEG power of such reactions was several times lower as compared to responses to positive signals, mainly, at the expense of the frequencies in the band of 90-225 Hz (the power of which was higher than that of the traditional band of 1-30 Hz and the gamma band of 30-80 Hz). The frequency composition of EEG reactions accompanying adequate responses was defined, mainly, by discrete subgroups of high-frequency components. During erroneous responses, the discrete structure of the corresponding EEG reactions was broken.

Animals↗

[Regional features of electrical reactions (in the frequency band of 1-225 Hz) in the cerebral cortex to conditioned stimuli in the course of instrumental conditioning].

Power spectra of short-term (less than 1 s) EEG-reactions (in the frequency band of 1-225 Hz) were studied in dogs in the course of instrumental food conditioning. These reactions were observed in different areas of the cortex in response to positive and differentiated conditioned stimuli. Regional features between the spectra were found both in the power level and frequency structure. The power of the reactions in the visual and parietal areas of the left hemisphere was higher than in the motor areas. Power spectra of reactions to differentiated stimuli were significantly lower than the spectra of reactions to positive stimuli mainly owing to the high-frequency components (80-225 Hz). In these both cases, prestimulus power spectra did not differ. The frequency structure of corresponding EEG-reactions consisted of individual spectral peaks, mainly both gamma (30-80 Hz) and higher-frequency (80-225 Hz) bands.

Animals↗

Interoceptive conditioning through repeated suppression of morphine-abstinence. I. Basis for conditioning: once-daily vs. continuous intravenous morphine infusion.

Experimental evaluation of Wikler's interoceptive conditioning hypothesis of relapse to opioid use in ex-addicts requires a preliminary study of the degree of physical dependence produced by two methods of drug administration. Wistar rats were made physically dependent on morphine by single daily intravenous injections or by a continuous i.v. infusion. Rats received the same total daily dose regardless of administration schedule. The initial daily morphine dose was 20 mg/kg, and was increased every fourth day by 20 mg/kg, until a dose of 200 mg/kg per day was reached. The rats were maintained at the highest dose level for 18 days, at which time morphine was discontinued. Body weight and water intake were the primary variables measured during addiction, maintenance, and abstinence phases of the study. Equivalent and parallel changes in mean weight and water intake in injection and infusion rats indicate equivalent degrees of physical dependence were developed. This finding allows separation of the contribution of conditioning factors and of protracted abstinence in facilitating opioid self-administration in formerly-dependent organisms.

Animals↗

Substitution of natural conditioned and unconditioned stimuli by artificial stimuli does not prevent acquisition of conditioned taste aversion in rats.

Attempts to replace a natural conditioned stimulus (taste) by electrical stimulation and a natural unconditioned stimulus (gastrointestinal disorder) by intracranial application of harmaline in the conditioned taste aversion (CTA) paradigm are described. The taste is replaced either by electrical stimulation of taste receptors of the tongue or by intracranial self-stimulation of the lateral hypothalamus, both triggered by licking. Both stimuli lose their rewarding properties when paired with gastrointestinal distress whereas self-stimulation triggered by nose poking is not affected by the same procedure. The unconditioned stimulus was replaced successfully by intracerebral injection of harmaline hydrochloride. The effect of the injection of 3-6 micrograms harmaline into the region of the inferior olive is comparable to that of systemic injection of 10 mg/kg harmaline. Electrophysiological analysis of the effect of locally and systemically applied harmaline indicates that the drug probably elicits CTA by activation of bulbar structures including the lateral reticular nucleus and lateral vestibular nucleus.

Animals↗

Extinction, reinstatement and spontaneous recovery of conditioned suppression in rats and the stability of conditioned inhibitor performance.

Acquisition of the suppressive properties of a conditioned stimulus (CS), terminating with shock, and of the attenuating properties of the conditioned inhibitor (CI), signaling that shock will not be given at the end of the CS, proceed at similar rates. The attenuation of suppression exerted by the CI and the decrement of the suppression due to extinction differed in both the time course and the distribution of barpresses within the CS duration. After extinction the CS still retained some suppressing properties, which were limited to the last 20-30 s, whereas the CI attenuated the suppression throughout the duration of the CS. Extinction of the suppressive properties of the CS did not change the attenuating properties of the CI. The recovery of the suppressive properties of the CS after presentations of unsignaled reinstating shocks or after a long pause in experimental sessions was incomplete and shortlasting. Both procedures did not change the properties of the CS presented in compound with the CI.

Animals↗

[The importance of involutively conditioned and conditioned by morbidity alterations of enteral absorption and the nutrition of geriatric patients with obstructive jaundice and carcinomatous diseases (author's transl)].

In case of absorption examinations in younger and advanced age it is necessary to differentiate between involutively conditioned alterations of enteral absorption and those ones conditioned by morbidity. For this purpose the modified D-xylose-absorption test offers itself as a diagnostical remedy. The equivalently characteristic alterations in absorption kinetics of carbohydrates in cases of the occurrence of an obstructive jaundice, in patients in the stage of generalisation of carcinomatous disease and in the elderly may be demonstrated by the modified D-xylose-Test.

Aged↗

[Situational conditioned reflexes in intact and callosotomized dogs when the location of conditioned and unconditioned stimuli is changed].

Positive and inhibitory conditioned reflexes were elaborated to signals, presented at the same display. Discrimination between spatially joined signals turned out to be a difficult task for intact and, in particular, for callosectomized dogs, who showed disturbances of the higher nervous activity. The analysis of spatially joined signals is possible for animals, previously trained in experiments with spatial separation of signals. With changed position of conditioned and unconditioned stimuli the callosectomized animals develop an inertness of nervous processes, manifested in a prolonged afteraction of the previously formed activity in an increased number of inadequate reactions, and impairment of differentiations.

Animals↗

[The interaction of homogeneous motor conditioned reflexes during conditioned-reflex switchover: the transfer of learning and interference].

The dynamics of elaboration of the conditioned switchover (CSw) of homogeneous motor conditioned reflexes (CR) with different lateralization of the motor skill was studied in rabbits. Learning of CSw was shown to pass three basic stages characterized by different degree of consolidation of the CRs, by interaction between the two CRs, and by manifestation of CSw. Stages I and II reflected the process of afferent and efferent generalization of CRs and CSw, stage III was associated with specialization of CRs and CSw. Both positive and negative transfer of motor learning as well as interference between the two motor skills took place during CSw elaboration. The highest rate of CSw acquisition was observed in rabbits displaying positive motor transfer.

Animals↗