Mediodorsal thalamic lesions and Pavlovian conditioning of heart rate and eyeblink responses in the rabbit.

Rabbits received ibotenic acid lesions of the mediodorsal nucleus of the thalamus (MD) or sham lesions. These animals were compared on 4 sessions of Pavlovian eyeblink and heart rate conditioning, in which a tone was the conditioned stimulus/stimuli (CS) and a paraorbital electrical shock was the unconditioned stimulus/stimuli (UCS). Lesions of MD retarded acquisition of the eyeblink conditioned response (CR) and abolished the late-occurring tachycardiac component of the heart rate CR. The data are compatible with previous experiments (H. Groenewegen, 1988), suggesting that MD participated in the sympathetic control associated with somatomotor learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Response rate and reinforcement rate in Pavlovian conditioning.

Four experiments used delay conditioning of magazine approach in rats to investigate the relationship between the rate of responding, R, to a conditioned stimulus (CS) and the rate, r, at which the CS is reinforced with the unconditioned stimulus (US). Rats were concurrently trained with four variable-duration CSs with different rs, either as a result of differences in the mean CS-US interval or in the proportion of CS presentations that ended with the US. In each case, R was systematically related to r, and the relationship was very accurately characterized by a hyperbolic function, R = Ar/(r +c). Accordingly, the reciprocal of these two variables—response interval, I (= 1/R), and CS-US interval, i (= 1/r) – were related by a simple affine (straight line) transformation, I = mi+b. This latter relationship shows that each increment in the time that the rats had to wait for food produced a linear increment in the time they waited between magazine entries. We discuss the close agreement between our findings and the Matching Law (Herrnstein, 1970) and consider their implications for both associative theories (e.g., Rescorla & Wagner, 1972) and nonassociative theories (Gallistel & Gibbon, 2000) of conditioning. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Intraseptal scopolamine has differential effects on Pavlovian eye blink and heart rate conditioning.

Evaluated the effects of intraseptal scopolamine hydrobromide (40 μg) injections on Pavlovian (classical) conditioning, with tones used as the CS and a periorbital electric shock train as the UCS, using New Zealand albino rabbits. Eyeblink (EB) and heart rate (HTR) CRs were concomitantly recorded. Although injections of scopolamine into the medial septum impaired the acquisition of the Pavlovian conditioned eyelid reflex, these injections enhanced the magnitude of accompanying Pavlovian conditioned HTR decelerations. However, scopolamine applied to the lateral septal area had no effect on EB conditioning, relative to the vehicle; like medial injections, scopolamine also enhanced the magnitude of the accompanying HTR decelerations. Results are compatible with those of previous investigations indicating that medial septal dysfunction impairs somatomotor conditioning but leaves autonomic conditioning intact and that septal dysfunction produces a parasympathetic bias of the cardiovascular system. (49 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hippocampectomy disrupts trace eye-blink conditioning in rabbits.

The role of the hippocampus (HPC) in trace eye-blink conditioning was evaluated using a 100-ms tone conditioned stimulus/stimuli (CS), a 300- or 500-ms trace interval, and a 150-ms air puff unconditioned stimulus/stimuli (UCS). Rabbits received complete hippocampectomy (dorsal & ventral), sham lesions or neocortical lesions. Hippocampectomy produced differential effects in relation to the trace interval used. With a 300-ms trace interval, HPC-lesioned Ss showed profound resistance to extinction after acquisition. With a 500-ms trace interval, HPC-lesioned Ss did not learn the task (only 22% conditioned responses [CRs] after 25 sessions, whereas controls showed >80% after 10 sessions), and on the few trials in which a CR occurred, most were "nonadaptive" short-latency CRs (i.e., they started during or just after the CS and always terminated prior to UCS onset). The authors conclude that the HPC encodes a temporal relationship between CS and UCS, and when the trace interval is long enough (e.g., 500 ms), that the HPC is necessary for associative learning of the conditioned eye-blink response. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Changes in heart rate levels during avoidance conditioning in the rabbit

During avoidance conditioning heart rate levels tend to increase or to decrease according to their initial values and these changes are not related to learning or performance of the task.     

GDNF improves dopamine function in the substantia nigra but not the putamen of unilateral MPTP-lesioned rhesus monkeys

Microdialysis measurements of dopamine (DA) and DA metabolites were carried out in the putamen and substantia nigra of unilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned rhesus monkeys that received intraventricular injections of vehicle or glial-derived neurotrophic factor (GDNF, 300 microg) 3 weeks prior to the microdialysis studies. Following behavioral measures in the MPTP-lesioned monkeys, they were anesthetized with isoflurane and placed in a stereotaxic apparatus. Magnetic resonance imaging (MRI)-guided sterile stereotaxic procedures were used for implantations of the microdialysis probes. Basal extracellular levels of DA and the DA metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were found to be decreased by >95% in the right putamen of the MPTP-lesioned monkeys as compared to normal animals. In contrast, basal DA levels were not significantly decreased, and DOPAC and HVA levels were decreased by only 65% and 30%, respectively, in the MPTP-lesioned substantia nigra. Significant reductions in d-amphetamine-evoked DA release were also observed in the MPTP-lesioned substantia nigra and putamen of the monkeys as compared to normal animals. A single intraventricular administration of GDNF into one group of MPTP-lesioned monkeys elicited improvements in the parkinsonian symptoms in these animals at 2-3 weeks post-administration. In addition, d-amphetamine-evoked overflow of DA was significantly increased in the substantia nigra but not the putamen of MPTP-lesioned monkeys that had received GDNF. Moreover, post-mortem brain tissue studies showed increases in whole tissue levels of DA and DA metabolite levels primarily within the substantia nigra in MPTP-lesioned monkeys that had received GDNF. Taken together, these data support that single ventricular infusions of GDNF produce improvements in motoric behavior in MPTP-lesioned monkeys that correlate with increases in DA neuronal function that are localized to the substantia nigra and not the putamen.     

Pavlovian conditioning with ethanol and lithium: Effects on heart rate and taste aversion in rats.

20 female albino Simonsen rats received paired injections of either ethanol or saline as the CS and LiCl as the UCS in a Pavlovian differential conditioning paradigm. LiCl evoked a large deceleration in heart rate (80–200 beats/min) as a UCR. As a result of 10 conditioning trials, the substance paired with LiCl elicited a lower average heart rate than that elicited by the unpaired substance. Moreover, Ss that received ethanol–LiCl injections subsequently were more averse to the taste of ethanol than Ss receiving saline–LiCl pairings. However, there were no differences in ethanol's ability to serve as the UCS to induce an aversion to a novel flavor solution (i.e., the Avfail phenomenon was not observed). The overall pattern of results underscores the value of using multiple indexes of learning in drug–drug conditioning paradigms. (21 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions of the cerebellar vermis and cerebellar hemispheres: Effects on heart rate conditioning in rats.

The effects of lesions of the cerebellum on the acquisition of heart rate (HR) conditioned responses (CRs) were examined in rats. Large lesions of the cerebellar vermis severely attenuated the acquisition of differentially conditioned bradycardic responses in restrained rats without affecting unconditioned HR responses to the tone conditioned stimuli (CSs) or the shock unconditioned stimulus/stimuli (UCS). In Exp 2, Ss were trained unrestrained, and under these conditions the CR was tachycardia in control Ss. Lesions of the vermis again severely attenuated acquisition of this CR without affecting unconditioned response (UCR) to the CSs or UCS. Bilateral lesions of the cerebellar hemispheres did not affect HR conditioning in either test procedure. The vermis of the cerebellum is an essential component of an HR conditioning circuit in the rat. The cerebellar hemispheres, which are involved in some discrete somatomotor CRs, have no essential functional contribution to HR conditioning. Results are discussed in relation to contributions from a forebrain system involved in HR conditioning and in relation to lateral cerebellar contributions to discrete somatomotor CRs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pavlovian conditioning of heart rate and body temperature with morphine: effects of CS duration

Rats were exposed to a conditioning procedure that varied the duration of overlap between a light-noise conditioned stimulus (CS) and the effects of a morphine (5 mg/kg) unconditioned stimulus (US). Three paired (P) groups differed in CS duration (5, 15, or 60 min) but had the same CS-US interval (30 s). A control group (U) received explicitly unpaired presentations of CS and US. P groups showed CS-specific attenuation of the bradycardic response and enhancement of the hyperthermic response to morphine. During placebo tests, the CS elicited conditioned increases in heart rate and body temperature in Groups P15 and P60. Group P5 showed a conditioned increase in heart rate but not in body temperature. Overall, strength of conditioning was directly related to CS duration. These data indicate that duration of overlap between a CS and drug-induced changes in a target response system is an important determinant of Pavlovian drug conditioning.     

Unblocking in Pavlovian appetitive conditioning.

Two experiments, with 280 Sprague-Dawley rats, demonstrated unblocking in an appetitive conditioning preparation. One stimulus, A, was first paired with either a low-value reinforcer (1 food pellet) or a high-value reinforcer (1 food pellet followed by 2 more food pellets). A 2nd stimulus, X, was then added to A, and the compound was reinforced with either the high- or low-value reinforcer. Conditioning to X was blocked if the same reinforcer was used in both phases of the experiment, but there was substantial conditioning to X when the reinforcer value was shifted either up or down when X was introduced. Exp I demonstrated this unblocking phenomenon using a design that minimized the potential contribution of generalization decrement. Exp II examined the effects of a variety of posttraining manipulations on conditioned responding to the added X cue after unblocking procedures. Among Ss that received downshifts in reinforcer value when X was introduced, responding was affected by several posttraining manipulations, including changes in context value. Those manipulations had smaller effects on the responding of Ss that received upshifts in reinforcer value and no effects on responding in control conditions. Findings are considered in relation to the model of conditioning outlined by R. A. Rescorla and A. R. Wagner (1972). (40 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Unblocking in Pavlovian fear conditioning.

Six experiments used rats to study blocking and unblocking of fear learning. An excitatory stimulus (A) blocked fear learning to a neutral stimulus (B). Unblocking of B occurred if the AB compound signaled an increase in unconditioned stimulus (US) intensity or number. Assessments of associative change during blocking showed that more was learned about B than A. Such assessments during unblocking revealed that more was learned about B than A following an increase in US intensity but not US number. These US manipulations had no differential effects on single-cue learning. The results show that variations in US intensity or number produce unblocking of fear learning, but for each there is a different profile of associative change and a potentially different mechanism. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The benzodiazepine midazolam does not impair Pavlovian fear conditioning but regulates when and where fear is expressed.

Rats were injected with a benzodiazepine (midazolam) and shocked after presentation of an auditory conditioned stimulus (CS). They were then tested for fear reactions (freezing) to the CS in either the original context or a 2nd context after either a short (1-day) or long (21-day) retention interval. Rats tested in the original context froze less after 1 day than rats tested after that interval in the 2nd context or rats tested after 21 days. Moreover, rats tested after the long interval in the original context froze less than rats tested after that interval in the 2nd context. Therefore, midazolam does not impair the acquisition of conditioned fear but regulates when and where that fear is expressed. These effects of midazolam were interpreted as a contextually controlled deficit in the expression of conditioned fear that is similar to that associated with latent inhibition and extinction (M. E. Bouton, 1993). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Haloperidol induces persistent down-regulation of tyrosine hydroxylase immunoreactivity in substantia nigra but not ventral tegmental area in the rat

The dopamine antagonist haloperidol can cause tardive side-effects that may persist after the drug is withdrawn. We studied the time course of changes in dopaminergic neurons of the substantia nigra and ventral tegmental area following withdrawal of haloperidol. Rats received daily intraperitoneal injections of saline or haloperidol for eight weeks and were killed at two, four or 12 weeks after the final injection. Sections of substantia nigra and ventral tegmental area were processed for tyrosine hydroxylase immunohistochemistry. Quantitative morphometric analysis was carried out blinded in order to determine the number, cell body size and topography of tyrosine hydroxylase-positive cells, and the immunoreactive area of the substantia nigra and ventral tegmental area. In haloperidol-treated rats, tyrosine hydroxylase-positive cell counts were normal in ventral tegmental area but were decreased in substantia nigra by 34% at two weeks withdrawal and by 52% at four weeks withdrawal; cell counts were almost fully recovered by 12 weeks withdrawal. Cross-sectional area of tyrosine hydroxylase immunoreactivity within the substantia nigra demonstrated a similar pattern of reduction, with full recovery by 12 weeks withdrawal. Mean cell size, by contrast, was essentially unchanged at two and four weeks withdrawal, but was significantly decreased in sub-regions of substantia nigra at 12 weeks withdrawal. These results indicate that haloperidol can produce selective changes in midbrain dopamine neurons that persist long after discontinuation of the drug. This decrease in tyrosine hydroxylase-immunoreactive cell counts may play a role in the neurobiology of the persistent tardive syndromes associated with the use of neuroleptics.     

Facilitation of appetitive Pavlovian conditioning by d-amphetamine in the shell, but not the core, of the nucleus accumbens.

The effects of postsession d-amphetamine within subregions of the ventral and dorsal striatum on appetitive Pavlovian learning were assessed. Rats acquired a conditioned approach response on presentation of a stimulus predictive of 10% sucrose solution (unconditioned stimulus [US]), but not during equally frequent presentations of a stimulus uncorrelated with the US. In Experiment 1, postsession d-amphetarnine infusions enhanced acquisition of conditioned responding, with no effect on control measures. In Experiment 2, rats received postsession d-amphetamine in the accumbens shell or core. Shell infusions facilitated conditioning; core infusions did not. In Experiment 3, dorsomedial striatal infusions of d-amphetamine also were ineffective. In sum, dopaminergic activation within the shell, but not the core, of the nucleus accumbens facilitates the acquisition of a Pavlovian association. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ethanol enhancement of Pavlovian conditioning.

60 New Zealand albino rabbits were tested for Pavlovian conditioning and extinction of eye-blink (EB) and heart-rate (HR) responses following water or various doses of oral ethanol (375–2,500 mg/kg). The highest dose suppressed both EB and HR conditioning during training, whereas the lowest dose enhanced HR responses during training and increased EB responses during later extinction in a symmetrically state-dependent manner. An intermediate dose (750 mg/kg) administered during training enhanced HR responses and suppressed EB responses but increased EB responses during later extinction following either ethanol or water. Ethanol treatments also suppressed unconditioned responses (UCRs) to shock and increased locomotor activity; however, these effects differed qualitatively from those that ocurred during Pavlovian training and extinction. Results suggest that very low doses of ethanol can enhance the ability of stimuli to elicit Pavlovian conditioned reflexes and impair the ability to adaptively modify these reflexes when stimulus contingencies later change. (55 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Marking effects in Pavlovian trace conditioning.

[Correction Notice: An erratum for this article was reported in Vol 13(3) of Journal of Experimental Psychology: Animal Behavior Processes (see record 2008-10750-001). The last sentence in the second paragraph of the Discussion on page 128 should read as follows: "A second possibility is that in the marked ITI group, the marking of irrelevant events in the middle of the intertrial interval promoted associations between those events and food, which then interfered with the learning of an association between SI and food."] In four experiments we investigated pigeons' acquisition of a successive discrimination with a trace autoshaping procedure. The conditioned stimuli were 5-s presentations of colored key lights, one of which was followed by food after a 5-s delay. In Experiment 1, which used spatially defined cues, we found that acquisition of differential responding to the reinforced cue was facilitated when a brief flash of light immediately followed both reinforced and nonreinforced cues. Experiment 2 found a similar enhancement by the added light flash in a purely visual discrimination. Experiment 3 found that the flash facilitated learning only when presented immediately after the discriminative cues, and not when it occurred immediately before the cues or at the time of reinforcement. A fourth experiment found this facilitation effect only when the flash and reinforcement occurred on the same trial. These results are interpreted in terms of marking: The flash enhanced learning because it triggered a backward scan through recent memory to search for possible predictors. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions of the midline thalamic nuclei impair classical conditioning under partial but not continuous reinforcement conditions

Protein Phosphatase-1 (PP-1) appears to be the key component of the insulin signalling pathway which is responsible for bridging the initial insulin-simulated phosphorylation cascade with the ultimate dephosphorylation of insulin sensitive substrates. Dephosphorylations catalyzed by PP-1 activate glycogen synthase (GS) and simultaneously inactivate phosphorylase a and phosphorylase kinase promoting glycogen synthesis. Our in vivo studies using L6 rat skeletal muscle cells and freshly isolated adipocytes indicate that insulin stimulates PP-1 by increasing the phosphorylation status of its regulatory subunit (PP-1G). PP-1 activation is accompanied by an inactivation of Protein Phosphatase-2A (PP-2A) activity. To gain insight into the upstream kinases that mediate insulin-stimulated PP-1G phosphorylation, we employed inhibitors of the ras/MAPK, PI3-kinase, and PKC signalling pathways. These inhibitor studies suggest that PP-1G phosphorylation is mediated via a complex, cell type specific mechanism involving PI3-kinase/PKC/PKB and/or the ras/MAP kinase/Rsk kinase cascade. cAMP agonists such as SpcAMP (via PKA) and TNF-alpha (recently identified as endogenous inhibitor of insulin action via ceramide) block insulin-stimulated PP-1G phosphorylation with a parallel decrease of PP-1 activity, presumably due to the dissociation of the PP-1 catalytic subunit from the regulatory G-subunit. It appears that any agent or condition which interferes with the insulin-induced phosphorylation and activation of PP-1, will decrease the magnitude of insulin's effect on downstream metabolic processes. Therefore, regulation of the PP-1G subunit by site-specific phosphorylation plays an important role in insulin signal transduction in target cells. Mechanistic and functional studies with cell lines expressing PP-1G subunit site-specific mutations will help clarify the exact role and regulation of PP-1G site-specific phosphorylations on PP-1 catalytic function.     

Studies of binaural detection in the rabbit (Oryctolagus cuniculus) with Pavlovian conditioning.

A Pavlovian conditioned eyeblink response in rabbits (Oryctolagus cuniculus) was used to study psychoacoustical phenomena previously demonstrated in human listeners and other animals. This article contains the results of a tone-in-noise detection study to examine 2 psychoacoustical phenomena in rabbit and in human listeners: (a) the binaural masking level difference (BMLD) and (b) differential performance across reproducible noise masker waveforms. The rabbits demonstrated a BMLD comparable in size to other species. Significant differences in performance across reproducible noise masker waveforms were seen in the rabbits. This performance was compared with the performance of human listeners using the same set of waveforms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Attenuation of self-stimulation from substantia nigra but not dorsal tegmental noradrenergic bundle by lesions of sulcal prefrontal cortex

Swallowed foreign bodies, fixed in the esophagus, are not uncommon in childhood. Their symptoms, complications, diagnosis and treatment are discussed. An expectant attitude is justified in regard to smaller fistulas and in big fistulas due to foreign bodies up to the remission of the localized inflammatory reaction. The present surgical methods are reviewed in the light of recent literature and a case study of a child cured by segmental resection of the trachea.