Aluminum-induced neurofibrillary degeneration disrupts acquisition of the rabbit's classically conditioned nictitating membrane response.

Rabbits received intraventricular injections of aluminum chloride, hydrochloric acid, or served as unoperated controls. On the 6th day postsurgery, they underwent 4 days (100 trials per day) of classical conditioning of the nictitating membrane response (NMR) to a tone conditioned stimulus and an air-puff unconditioned stimulus. Unoperated and hydrochloric acid control animals readily acquired the conditioned response. Aluminum intoxicated rabbits, in contrast, did not acquire the conditioned response over the 4 days of testing. This disruption of conditioning in aluminum-treated rabbits could not be attributed to deficits in sensory or motor processes or to illness. Neuropathological analysis revealed widespread neurofibrillary tangle formation in aluminum-treated animals. Furthermore, the degree of neurofibrillary degeneration was significantly negatively correlated with the degree of conditioning. The results are considered in the context of using the rabbit NMR preparation as a model system for studying age-related conditioning disorders. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Early acquisition, but not retention, of the classically conditioned eyeblink response is N-methyl-D-aspartate (NMDA) receptor dependent

N-methyl-D-aspartate (NMDA) antagonists impair performance in some tasks, but whether they impair learning directly or through effects on sensorimotor performance remains controversial. Rats administered a competitive NMDA antagonist, CGP-39551, 24 hr before training could not acquire a classically conditioned eyeblink response. The associative deficit remained evident during training with a high-intensity conditioned stimulus, even though sensory reactivity was unaffected. The antagonist did not alter retention and thus did not affect motor performance of the task. These results extend and confirm studies that implicate NMDA-receptor activation in the acquisition of classically conditioned associations and specifically in tasks not dependent on the hippocampus for learning itself. Moreover, they substantiate recent claims that NMDA receptor activation (and by association, long-term potentiation) may be involved in early processes of procedural memory formation.     

Phenytoin blocks the reversal of a classically conditioned discriminative eyeblink response in rabbits

The aim of the present study was to assess the role of vascular alpha 1D-adrenoceptors in the sympathetic vasopressor response in vivo. Specifically, we evaluated the effect of a selective alpha 1D-adrenoceptor antagonist, BMY 7378 (8-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-8-azaspiro(4,5)dec ane-7,9- dione 2HCl), on the vasopressor response induced by preganglionic (T7-T9) sympathetic stimulation in the pithed rat. The vasopressor response was dose-dependently sensitive to inhibition by intravenous BMY 7378 (0.1, 0.31, 1 and 3.1 mg/kg), doses of 1 and 3.1 mg/kg being equally effective. Like BMY 7378, 5-methylurapidil (0.1, 0.31, 1 and 3.1 mg/kg) antagonized the vasopressor response to spinal stimulation; doses of 1 and 3.1 mg/kg were also equally effective. In combination experiments, BMY 7378 (1 mg/kg, i.v.) and the alpha 1A-adrenoceptor antagonist, 5-methylurapidil (1 mg/kg, i.v.), showed an additive effect. The present results demonstrate that the alpha 1D-adrenoceptor subtype plays an important role in the pressor response to sympathetic nerve stimulation in the pithed rat, and confirm the participation of the alpha 1A-adrenoceptor subtype in the same response.     

Long-term retention of the classically conditioned eyeblink response in rats.

Retention of the classically conditioned eyeblink response in rats was tested with a conditioned stimulus (CS)-alone extinction test and 2 sessions of reacquisition training. Retention of the eyeblink conditioned response (CR) during both tests was highest 24 hrs and 1 mo after initial acquisition. Three months after initial acquisition, responding during the CS-alone test was at baseline, but there was significant savings during reacquisition. By 6 mo after initial acquisition, the memory for the eyeblink CR was not expressed in either test. The group differences in retention, despite initial acquisition of the eyeblink CR to equal levels, suggest that rat eyeblink conditioning may provide a useful behavioral model for studying the neural processes underlying memory retention and loss. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Clonidine blocks acquisition but not expression of conditioned opiate withdrawal in rats

Previous studies in rodents have reported that clonidine, an alpha 2-adrenergic receptor agonist, attenuated conditioned aversions to naloxone-precipitated opiate withdrawal when administered prior to each withdrawal conditioning episode. The current study was designed to determine whether clonidine could modify the expression of previously established conditioned place aversions and conditioned suppression of operant responding. Dose- and time-dependent effects of clonidine on activity and suppression of operant responding for food identified appropriate treatment parameters for subsequent studies in which rats rendered dependent on opiates through implantation of morphine pellets were tested for: (1) conditioned place aversion; and (2) conditioned suppression of operant responding for food (fixed ratio-15 schedule), in a paradigm wherein rats received four pairings of naloxone with a distinct tone and odor stimulus. Clonidine dose-dependently blocked the acquisition of both conditioned behaviors when administered prior to naloxone on each conditioning trial, but was ineffective in blocking the expression of these conditioned withdrawal signs when administered prior to the test session.     

Lesions of the middle cerebellar peduncle disrupt acquisition and retention of the rabbit's classically conditioned nictitating membrane response.

Rabbits were classically conditioned to emit a nictitating membrane response (NMR) to either a light or tone conditioned stimulus (CS) paired with an eye shock unconditioned stimulus (UCS). They then received lesions of the middle cerebellar peduncle (MCP) or served as unoperated controls. Following surgery, they were given separate presentations of tone, light, and vibratory CSs, each paired with the eye shock UCS. In this way, conditioned responses (CR) to the previously trained light or tone served as a test of retention, whereas CRs to the remaining two conditioned stimuli (tone and vibratory or light and vibratory) served as a test of acquisition. The results of the study revealed that rabbits with complete lesions of the MCP showed disrupted acquisition and retention of the conditioned NMR to all stimuli, rabbits with partial MCP lesions also showed disrupted acquisition and retention to all CSs, but to a lesser degree, and animals with lesions that missed the MCP and unoperated controls both showed normal acquisition and retention of the conditioned NMR. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hippocampus and trace conditioning of the rabbit's classically conditioned nictitating membrane response.

In 2 experiments, 36 New Zealand albino rabbits received classical conditioning of the nictitating membrane response in a trace conditioning paradigm. In this paradigm, a 250-msec tone conditioned stimulus (CS) occurred, after which there was a 500-msec period of time in which no stimuli occurred (the trace interval), followed by a 100-msec air-puff unconditioned stimulus (UCS). In Exp I, lesions of the hippocampus or cingulate/retrosplenial cortex (CRC) disrupted acquisition of the long-latency or adaptive conditioned response (CR) relative to unoperated controls and Ss that received neocortical lesions that spared the CRC. When Ss with hippocampal or CRC lesions were switched to a standard delay paradigm in which the CS and UCS were contiguous in time, they acquired in about the same number of trials as naive Ss. In Exp II, multiple-unit activity in area CA1 of the hippocampus was examined during acquisition of the trace CR. Ss had a 500-msec trace interval (Group T-500), received explicitly unpaired presentations of the CS and UCS, or underwent conditioning with a 2-sec trace interval. Group T-500 acquired the CR in about 500 trials. Early in training, there was a substantial increase in neuronal activity in the hippocampus that began during the CS and persisted through the trace interval. Later in conditioning as CRs emerged, the activity shifted to later in the trace interval and formed a model of the amplitude–time course of the behavioral CR. (65 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acquisition of the classically conditioned eyeblink response in humans over the life span.

Human subjects ranging in age from 18 to 85 years underwent classical conditioning of the eyeblink response to a tone conditioned stimulus (CS) and an air-puff unconditioned stimulus (UCS). There was a decline in percentage of conditioned responses with age. This decline was most noticeable in subjects over age 50. These conditioning deficits were not due to age-related changes in sensitivity to the tone CS or the air-puff UCS, nor could the conditioning deficits be attributed to an age-related decline in general cognitive abilities or to changes in spontaneous blink rates. The results are discussed in terms of using the classically conditioned eyeblink in humans in conjunction with the classically conditioned nictitating membrane response in rabbits as a model system for studying the neurobiology of age-related conditioning deficits. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spontaneous recovery but not reinstatement of the extinguished conditioned eyeblink response in the rat.

Reinstatement—the return of an extinguished conditioned response (CR) after reexposure to the unconditioned stimulus (US)—and spontaneous recovery—the return of an extinguished CR with the passage of time—are 2 of 4 well-established phenomena that demonstrate that extinction does not erase the conditioned stimulus (CS)–US association. However, reinstatement of extinguished eyeblink CRs has never been demonstrated, and spontaneous recovery of extinguished eyeblink CRs has not been systematically demonstrated in rodent eyeblink conditioning. In Experiment 1, US reexposure was administered 24 hr prior to a reinstatement test. In Experiment 2, US reexposure was administered 5 min prior to a reinstatement test. In Experiment 3, a long, discrete cue (a houselight), present in all phases of training and testing, served as a context within which each trial occurred to maximize context processing, which in other preparations has been shown to be required for reinstatement. In Experiment 4, an additional group was included that received footshock exposure, rather than US reexposure, between extinction and test, and contextual freezing was measured prior to test. Spontaneous recovery was robust in Experiments 3 and 4. In Experiment 4, context freezing was strong in a group given footshock exposure but not in a group given eye shock US reexposure. There was no reinstatement observed in any experiment. With stimulus conditions that produce eyeblink conditioning and research designs that produce reinstatement in other forms of classical conditioning, we observed spontaneous recovery but not reinstatement of extinguished eyeblink CRs. This suggests that reinstatement, but not spontaneous recovery, is a preparation- or substrate-dependent phenomenon. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Ontogeny of the conditioned eyeblink response in rats: acquisition or expression?

Eyeblink conditioning depends critically on an identified brainstem-cerebellar circuit and is modulated under some circumstances by the hippocampus, amygdala, and other forebrain regions. Developmental studies of eyeblink conditioning could help elucidate questions concerning the behavioral expression of plasticity within these brain circuits and regions, and of their functional interactions, as they unfold during ontogeny. Recently, this laboratory has shown that conditioning of the eyeblink reflex develops dramatically between Postnatal Days (PND) 17 and PND 24 in the rat. The present study asked whether the developmental emergence of the eyeblink conditioned response (CR) occurs gradually or abruptly over this age range, and whether it reflects developmental changes in acquisition or expression of the learned eyeblink reflex. In Experiment 1, rat pups received two consecutive days of training beginning on PND 17, 20, or 24. Conditioned responses occurred at low levels on PND 17-18, intermediate levels on PND 20-21, and high levels on PND 24-25. In Experiment 2, 17-day-old rats received 2 days of training, 72 h apart, so that effects of training on PND 17 could be examined at an age, PND 20, when expression of the eyeblink CR was clearly possible. On PND 20, rat pups that had received paired training on PND 17 showed significantly faster conditioning than controls that had received unpaired training or no training on PND 17. These findings suggest that neural plasticity underlying associative learning developmentally precedes its overt expression in behavior. Hypotheses concerning the nature and locus of this learning are discussed.     

Modulation of the acquisition of the rabbit eyeblink conditioned response by conditioned contextual stimuli.

Three experiments were conducted to ask if conditioned emotional responses (CERs) controlled by contextual cues modulate the acquisition of eyelid conditioned responses (CRs) to discrete conditioned stimuli (CSs). Experiment 1 showed that 30-s auditory stimuli that were paired with aversive shocks to one paraorbital region or the other controlled discriminated CERs, as measured by potentiation of a startle response. In Experiments 2 and 3, similarly trained 30-s stimuli served as contexts in which 1,050-ms CSs were paired with a paraorbital unconditioned stimulus (US). Reinforced contexts both impaired (Experiments 2A and 2B) and facilitated (Experiment 3B) acquisition of the eyeblink CR, depending on the locus of the USs involved. The data are consistent with the interpretation that CERs controlled by contextual cues facilitate CR acquisition, but do so in the face of blocking effects of CR tendencies also conditioned to the contextual cues. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Shortened conditioned eyeblink response latency in male but not female Wistar-Kyoto hyperactive rats.

Reductions in the volume of the cerebellum and impairments in cerebellar-dependent eyeblink conditioning have been observed in attention-deficit/hyperactivity disorder (ADHD). Recently, it was reported that subjects with ADHD as well as male spontaneously hypertensive rats (SHR), a strain that is frequently employed as an animal model in the study of ADHD, exhibit a parallel pattern of timing deficits in eyeblink conditioning. One criticism that has been posed regarding the validity of the SHR strain as an animal model for the study of ADHD is that SHRs are not only hyperactive but also hypertensive. It is conceivable that many of the behavioral characteristics seen in SHRs that seem to parallel the behavioral symptoms of ADHD are not solely due to hyperactivity but instead are the net outcome of the interaction between hyperactivity and hypertension. We used Wistar-Kyoto Hyperactive (WKHA) and Wistar-Kyoto Hypertensive (WKHT) rats (males and females), strains generated from recombinant inbreeding of SHRs and their progenitor strain, Wistar-Kyoto (WKY) rats, to compare eyeblink conditioning in strains that are exclusively hyperactive or hypertensive. We used a long-delay eyeblink conditioning task in which a tone conditioned stimulus was paired with a periorbital stimulation unconditioned stimulus (750-ms delay paradigm). Our results showed that WKHA and WKHT rats exhibited similar rates of conditioned response (CR) acquisition. However, WKHA males displayed shortened CR latencies (early onset and peak latency) in comparison to WKHT males. In contrast, female WKHAs and WKHTs did not differ. In subsequent extinction training, WKHA rats extinguished at similar rates in comparison to WKHT rats. The current results support the hypothesis of a relationship between cerebellar abnormalities and ADHD in an animal model of ADHD-like symptoms that does not also exhibit hypertension, and suggest that cerebellar-related timing deficits are specific to males. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Subicular lesions disrupt but do not abolish classically conditioned bradycardia in rabbits.

Rabbits and rats received horseradish peroxidase injections in the medial prefrontal cortex. and retrograde labeling was examined in the hippocampus (HC) and subicular complex (SC). Labeled cells were observed in HC and SC in the rat, but only in the SC of the rabbit. In a second experiment, separate groups of rabbits with sham, SC, or cortical control lesions were subjected to differential classical heart rate conditioning, in which 4-s, 75-db tones served as conditioned stimuli and a 3-mA paraorbital shock was the unconditioned stimulus. Although conditioned bradycardia was obtained in animals with SC lesions, it was slower to develop and was much shorter in duration than in the cortical and sham control groups. In the animals with SC lesions, the bradycardiac response was quickly replaced with tachycardia, suggesting a sympathetic bias in these animals. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acquisition of a second-order classically conditioned response.

Following alleyway food-training on a 50% random partial reinforcement schedule and 10 forward 1st-order (CS1-UCS) conditioning trials elsewhere, forward 2nd-order (CS2-CS1) classical conditioning trials were initiated for 40 female albino rats (Group 1) and equivalent but backward (CS1-CS2) training was started for 20 additional Ss (Group 2). After each set of 2 CS1-UCS and 3 CS2-CS1 trials (or 3 CS1-CS2 trials for Group 2) were given, the CS2 was presented in the goal area of the alley on nonreinforced trials to assess its suppressing effect on total running times. While the performance of Group 2 to the CS2 was unchanged as a function of conditioning trials, Group 1 evinced both increasing suppression and skin conductance levels as 2nd-order training progressed. Maximum suppression was obtained by the 12th CS2-CS1 trial. (French summary) (16 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Five-year retention of the classically conditioned eyeblink response in young adult, middle-aged, and older humans

OBJECTIVE: To describe the clinical profile of demyelinating optic neuritis in African Americans. METHODS: The medical records of all patients with a diagnosis of optic neuritis examined at the Neuro-Ophthalmology Unit at the Emory University Eye Center (Emory) and at the Grady Memorial Hospital Eye Clinic (Grady), Atlanta, Ga, between 1989 and 1996 were retrospectively reviewed. PATIENTS: African American and white patients, aged 15 through 55 years, with a single initial episode of acute optic neuritis of unknown or demyelinative origin were included in the study. Study patients included 23 African American patients and 56 white patients examined at Emory as well as 10 African American patients examined at Grady. RESULTS: There were no significant differences among the African American study patients, the white study patients, and patients from the Optic Neuritis Treatment Trial (ONTT) regarding sex (P=.36), age (P=.73), or the presence of disc edema (P=.40), lesions found on magnetic resonance imaging (P=.43), or multiple sclerosis (P=.54) at the onset of an initial episode of optic neuritis. The Emory African American patients presented with more frequent severe visual loss (13 [93%] of 14 patients with a visual acuity < or =20/200) compared with Emory white patients (12 [39%] of 31 patients; P=.002) and with ONTT patients (161 [36%] of 448 patients; P<.001). At follow-up examination of at least 1 year, Emory African American patients had worse vision (9 [39%] of 23 patients <20/40, and 4 [17%] of 23 patients < or =20/200) compared with Emory white patients (5 [8%] of 63 patients <20/40, P=.001; 3 [5%] of 63 patients < or =20/200, P=.08), and with ONTT patients (29 [7%] of 409 patients <20/ 40, P=.0001; 12 [3%] of 409 patients < or =20/200, P=.01). Compared with ONTT patients, the Emory African American patients combined with the Grady African American patients had more frequent severe visual loss (visual acuity < or =20/200) at presentation (18 [90%] of 20 patients vs 161 [36%] of 448 patients; P<.001) and at follow-up examination of at least 1 year (6 [18%] of 33 patients vs 12 [3%] of 409 patients; P=.002). Seven (58%) of 12 African American patients with multiple sclerosis had a "neuromyelitis optica" presentation defined by the presence of neurological deficits limited to the optic nerves and spinal cord. CONCLUSIONS: The African American study patients with a single episode of demyelinating optic neuritis had visual acuities more severely affected at onset and after 1 year of follow-up compared with the white study patients and with patients in the ONTT. In the African American patients, multiple sclerosis occurred most frequently in a "neuromyelitis optica" form.     

Extraversion and the acquisition of eyeblink and GSR conditioned responses.

A summary is given of studies relating eyeblink and GSR conditioning to the personality dimension of extraversion (E). It is found that extraverts are poorer in eyeblink conditioning when conditions favor the development of inhibition, as by the use of partial reinforcement; they do not differ from introverts when conditions are such as to preclude the development of inhibition. Extraverts are poorer in GSR conditioning when relatively mild stimuli are used, but do not differ from introverts when very strong stimuli are used, making impossible the development of cortical inhibition. They are also poorer than introverts when discrimination learning is involved, facilitating the growth of inhibition. Correlations between conditioning and personality appear to be dependent on the suitability of experimental conditions to evoke cortical inhibition; correlations are process and not status functions. These findings have implications for the problem of the generality of the hypothetical factor of "conditionability." (2 p. ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Intra-amygdala infusion of the N-methyl-D-aspartate receptor antagonist AP5 blocks acquisition but not expression of fear-potentiated startle to an auditory conditioned stimulus.

The fear-potentiated startle paradigm, in which the amplitude of the startle reflex is enhanced in the presence of a stimulus previously paired with footshock, was used to measure aversive conditioning after intra-amygdala infusion of the competitive N-methyl-{d}-aspartate (NMDA) receptor antagonist {dl}-2-amino-5-phosphonopentanoic acid (AP5). Infusion of 2.5 μg/side AP5 immediately before 5 noise–footshock pairings on each of 2 consecutive days dose-dependently blocked acquisition or consolidation of auditory fear-potentiated startle, consistent with previous results obtained with a visual stimulus. Somatosensory or auditory transmission deficits do not appear to be induced by intra-amygdala AP5, because rats reacted normally to footshocks and showed reliable potentiated startle expression after pretesting AP5 infusion at a dose that blocked acquisition. Together with earlier reports, these data suggest that an NMDA-dependent process localized in or near the amygdala may be necessary for the acquisition of conditioned fear across different sensory modalities. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Trial distribution effects on postasymptotic performance and retention of the rabbit's (Oryctolagus cuniculus) classically conditioned nictitating membrane response.

Conditioned the nictitating membrane response to asymptote under identical experimental parameters in 3 groups of albino rabbits (N = 36). Subsequently, the 1st group was shifted to a longer modal intertrial interval (ITI) for further training, the 2nd group was switched to a shorter modal ITI, and the 3rd group was continued with intermediate ITI values. Results reveal (a) immediate incremental and decremental performance adjustments following the shift to longer and shorter modal ITIs, respectively, which were maintained over 10 postasymptotic sessions; (b) evidence of within-session performance decrements during postasymptotic conditioning; and (c) no evidence of retention losses in a retention test conducted 72 hr following the final conditioning session. (16 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Naloxone facilitates extinction but does not affect acquisition or expression of ethanol-induced conditioned place preference.

Mice (DBA/2J) received a Pavlovian procedure in which a distinctive floor stimulus was paired 4 times with ethanol (2 g/kg). A different floor stimulus was paired with saline. Naloxone (0.0, 1.5, or 10.0 mg/kg, intraperitoneal) given before each ethanol trial did not interfere with acquisition of conditioned preference, although naloxone alone produced conditioned aversion. When naloxone (0.0, 0.15, 1.5, 3.0, or 10.0 mg/kg) was given for the first time during testing, mice showed conditioned preference during the first 10 min. However, preference subsequently decreased dose-dependently over time. Control studies eliminated alternative interpretations based on pharmacokinetics or presence of an aversive state. The overall pattern of results suggests that naloxone facilitated extinction of conditioned place preference and supports the hypothesis that ethanol-induced conditioned reinforcement is mediated by the endogenous opioid system. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Attention is required for acquisition but not expression of new response biases.

Throughout a lifetime of interaction with the physical environment, people develop a strong bias to respond on the same side as the location of a target object, even when its location is irrelevant to the task at hand. Recent research has shown that this compatibility bias can be overridden with relatively brief but focused training. To better understand how such training affects preexisting response biases, we investigated whether attention is required to acquire and express a new bias to respond on the opposite side, thus creating an incompatibility bias. Participants practiced making responses on the opposite side from left and right tones and then made responses based on the frequencies (high or low) of the same tones. As in previous research, practice with a spatially incompatible mapping eliminated the compatible bias in the Simon task. The addition of an attention load (continuous secondary tracking task) during practice prevented learning the new response bias. However, once the new bias was learned, it overrode the compatibility bias regardless of available attentional resources. We suggest that not only can a quickly learned response bias overwhelm preexisting biases that are acquired over years of experience but that recently learned and older, preexisting biases are similarly affected by attention load. (PsycINFO Database Record (c) 2010 APA, all rights reserved)