Responses of dorsal column nuclei neurons in rats with experimental mononeuropathy

During nerve cell degeneration, cholesterol released from the degrading cells is conserved through the formation of a cholesterol-apolipoprotein (apo) E complex which is subsequently taken up by regenerating nerve cells. The aim of the present project was to identify the physiologically relevant lipoprotein receptor for this lipoprotein complex which has remained elusive. HDL was separated into apo E-rich and apo E-poor subfractions and labelled with [14C]-sucrose. Labelled apo E-rich HDL bound to rat brain membranes in a time- and ligand concentration-dependent manner and was a saturable process. Essentially no binding occurred with [14C]-apo E-poor HDL or with free apo E. Binding was partially inhibited by low density lipoprotein (LDL) and by alpha 2-macroglobulin. These results provide new evidence that native apoE-rich HDL particles resembling those present in the brain bind to rat brain membranes and that the binding may be due, at least in part, to the LDL receptor and to the LDL-receptor related protein. Evidence was also provided for the presence of a receptor which binds [14C]-sucrose human apoE-rich HDL in human brain. Characterisation of the receptor which mediates the uptake of cholesterol from HDL-like complexes by brain cells is important in understanding the role of apoE in the central nervous system and of the alterations which occur in disorders such as Alzheimer's disease.     

Forelimb performance by squirrel monkeys (Saimiri sciureus) before and after dorsal column lesions.

Old World monkeys with dorsal column lesions have exhibited slow, inept reaching movements in extrapersonal space under neurological examination. The purpose of the present study was to obtain quantified observations of such performance in similarly prepared squirrel monkeys. Nine young adult Ss with high cervical lesions of the dorsal columns were tested pre- and postoperatively. After preoperative testing, 3 Ss were assigned as controls. Experimental Ss were compared with sham-operated controls on 3 tests requiring fast reaching for stationary bait and on 1 test requiring catching of a falling bait. Experimental Ss were impaired relative to controls postoperatively only on bait catching. Possible reasons for the apparent discrepancy between the forelimb performance of New World monkeys and Old World monkeys are discussed. (26 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Preoperative differential housing and dorsal hippocampal lesions in rats.

The resemblance between the effects of social isolation and of hippocampal lesions (HCLs) in rats led to a study that investigated whether rats socially isolated at weaning rather than grouped counterparts show less behavioral change after sustaining dorsal HCLs when adults. Ss were 8 grouped male Lister rats with HCLs, 8 grouped male controls, 8 isolated male with HCLs, and 8 isolated controls. In socially reared Ss, HCLs produced increased ambulation and object contact in an open field, reduced passive avoidance in a runway task, and produced faster acquisition of active avoidance in a shuttlebox, but there were no such differences in isolation-reared Ss. Ambulation and object contact in isolates were intermediate to those of HCL Ss and intact group-housed Ss, and the behavior of isolates during passive and active avoidance training was generally similar to that of grouped Ss with HCLs. The introduction of a distractor during approach training in an alley reduced running speeds more in Ss with HCLs than in controls. The significant interactions between housing and lesion state suggest that neural pathways associated with the hippocampal formation may mediate some behavioral effects of differential housing. (41 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Radial-arm maze behavior by rats with dorsal hippocampal lesions: Effects of cuing.

In 4 experiments with 180 male Wistar and Long-Evans rats, Ss with bilateral dorsal hippocampal lesions were impaired when tested on standard (noncued) versions of the radial-arm maze, but other hippocampal groups performed almost as well as cortical and operated control groups when salient visual cues were added to each arm. Preoperative training on the noncued, but not the cued, maze interfered with the benefits of postoperatively cuing hippocampal groups. Control groups performed equally well under all cuing and training conditions. Procedures that eliminated response sequencing did not affect performance of hippocampal or control groups. Results are interpreted as reflecting hippocampal involvement in mediating spatial cues, but not necessarily along the lines predicted by cognitive map theory. It is suggested that deficits of animals with hippocampal lesions represent 1 manifestation of a general impairment in processing information. (39 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Illness-induced context aversion learning in rats with lesions of the dorsal hippocampus

In 2 experiments, rats with electrolytic lesions of the dorsal hippocampus and sham-operated control subjects were given injections of lithium chloride after exposure to a distinctive context. This procedure establishes a context-illness association in intact subjects. In Experiment 1, the strength of the context aversion was assessed by measuring the subjects' willingness to consume a novel flavor in the context. It was found that lesioned subjects showed less suppression of consumption than controls. Experiment 2 tested the ability of the context to block subsequent flavor-aversion learning and revealed less effective blocking in lesioned rats. These results are consistent with the view that hippocampal lesions retard context conditioning; unlike previous work that has made use of conditioned freezing as the measure of context conditioning, the present results are not explicable in terms of lesion-induced changes in general activity.     

Contextual control of conditioned responding in rats with dorsal hippocampal lesions.

The control exerted by contextual cues over classically conditioned responding was assessed for rats with electrolytic lesions of the dorsal hippocampus and sham-operated controls. In 3 experiments the rats received initial training with 2 reinforced cues, each presented in its own distinctive context, followed by a nonreinforced test in which the cues were presented in the other context. Both control and operated subjects showed context specificity, as evidenced by less vigorous responding to these cues than to cues presented on test in their original contexts. The groups did not differ in their ability to learn an explicit discrimination in which a given cue was reinforced in one context and nonreinforced in a different context (although the groups did differ on a simple autoshaping task). It is concluded that a special role for the hippocampus in the contextual control of conditioned responding still remains to be demonstrated. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of melatonin on the heart rate variability caused by lesions of the dorsal hippocampus in rats

Bilateral lesions of the hippocampus induced irregular shifts of the heart rate variability in rats. The shifts could be prevented with melatonin but not with diazepam.     

Disruption of spatial but not object-recognition memory by neurotoxic lesions of the dorsal hippocampus in rats.

Ischemia-induced cell loss in the CA1 region of the dorsal hippocampus results in severe deficits on delayed non-matching-to-sample (DNMS), whereas hippocampectomy produces little or no impairment, suggesting that partial hippocampal damage is more detrimental to DNMS performance than total ablation. To test this hypothesis, rats with or without preoperative DNMS training were given partial cytotoxic lesions of the dorsal hippocampus. When tested, neither group displayed any DNMS deficits despite widespread cell loss in the CA1 and other regions of the dorsal hippocampus. In the final experiments, rats tested previously on DNMS were found to be impaired on the Morris water maze. The finding that partial hippocampal lesions disrupt spatial memory while leaving object-recognition memory intact indicates a specialized role for the hippocampus in mnemonic processes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Intact selective attention in rats with lesions of the dorsal noradrenergic bundle.

Tested S. T. Mason's hypothesis (1980) that lesions of the dorsal noradrenergic bundle (DNB), which induce depletion of forebrain noradrenaline, alter performance of discrimination tasks because they retard habituation to naturally attractive, but instrumentally irrelevant, stimuli. Exp I used 100 male Wistar rats in groups with either vehicle or 6-hydroxydopamine injections into the DNB. Groups were assigned to 5 discrimination tasks in a cross-maze. Lesions of the DNB did not alter performance of any of the tasks. In Exp II, control and noradrenaline-depleted Ss were trained in a task of light–dark discrimination followed by shift to position discrimination in a Y-maze. At the onset of training, Ss of both groups reliably avoided the bright goal arm and responded to the dark arm, thus demonstrating predominant attention for the relevant brightness stimuli rather than the irrelevant position stimuli. DNB lesions impaired acquisition of brightness discrimination only when the positive stimulus was the illuminated goal arm, and they did not alter shift performance. These results do not support Mason's hypothesis; but on the other hand they do indicate that DNB lesions in the rat can impair habituation of light avoidance. (25 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Failure of seriatim dorsal hippocampal lesions to spare spatial reversal behavior in rats.

Notes that the assessment of unaided functional sparing following sequential lesions has usually involved either neocortically controlled learned behaviors or nonneocortically controlled unlearned behaviors. Typically, the learned behaviors are protected by the seriatim operative procedure but the unlearned behaviors are not. This pattern of results could be a function of either the involved behavior (learned vs. unlearned) or the brain area mediating the behavior (neocortical vs. nonneocortical). In an attempt to distinguish between these 2 possibilities, a hippocampally controlled learned response was used to assess the occurrence of unaided functional sparing following sequential, spaced lesions in 30 male hooded rats. Results give no indication that the learned response was spared by the seriatim operative procedure even when the Ss were provided interlesion remedial training. (21 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Allocentric spatial and tactile memory impairments in rats with dorsal caudate lesions are affected by preoperative behavioral training.

Rats with caudate lesions and pretrained for 36 trials demonstrated impaired performance on the "reference memory" or invariant aspect of a 12-arm maze and normal performance on the "working memory" or variable aspect of the maze. Rats with caudate lesions and no pretraining were also impaired on an invariant tactile discrimination in a T maze, but they were not impaired on the variable goal-arm choice of the T maze. More extensive preoperative training ameliorated behavioral deficits of rats with caudate lesions in the T maze and radial arm maze. Results showed that behavioral impairment after damage to the caudate is not restricted to egocentric tasks as previously suggested, but the caudate seems to be involved in the initial acquisition that is invariant over many trials. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Adenosine mediates spinal norepinephrine-produced antinociception as revealed by nociceptive discharges in parafascicular neurons in rats

The effects of intrathecal pretreatment with aminophylline on intrathecal norepinephrine-produced or serotonin-produced suppression of noxiously evoked discharges in thalamic parafascicular neurons were investigated in 35 urethane-anesthetized rats. The results showed that: (1) both intrathecal norepinephrine (15 nmol) or serotonin (20 nmol) produced significant suppression of noxiously evoked discharges in parafascicular neurons; (2) intrathecal aminophylline (120 nmol) blocked the norepinephrine-produced suppression of noxiously evoked discharges, while the same dose of aminophylline exhibited no significant effect on the serotonin-produced suppression of these discharges in parafascicular neurons. The results suggest that spinal norepinephrine-produced, but not serotonin-produced, antinociceptive effects may be mediated by adenosine as one of successive chemical links in the spinal dorsal horn circuitry.     

Medial dorsal thalamic lesions impair blocking and latent inhibition of the conditioned eyeblink response in rats.

The effects of lesions of the medial dorsal thalamic nucleus (MD) on blocking and latent inhibition (LI) of the rat eyeblink response were examined in the present study. Previous work has demonstrated that the cingulate cortex and related thalamic areas are involved in processing conditioning stimuli throughout training. The experiments in the present study tested the hypothesis that disruption of cingulothalamic stimulus processing produced by lesions of the MD would impair 2 types of associative learning that involve decremental changes in attention. In Experiment 1, MD lesions severely impaired blocking. In Experiment 2, NM lesions severely impaired LT. The results indicate that lesions of the NM impair incremental, decremental, or both types of changes in stimulus processing during learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Naloxone-reversible antinociception by paracetamol in the rat

Paracetamol at the dose of 400 mg/kg i.p. displayed antinociceptive activity in the hot-plate test and the formalin test. Moreover, it induced a significant increase in brain serotonin (5-HT) concentration and a reduction in the number of 5-HT2 receptors in cortical membranes. Pretreatment with naloxone abolished this antinociceptive activity both in the hot-plate test and in the first phase of the formalin test without affecting the serum concentration of paracetamol. At the same time, naloxone prevented the increase in 5-HT concentration in the central nervous system and the reduction in 5-HT2 receptors in cortical membranes. Competition experiments demonstrated that paracetamol possesses affinity for [3H]naloxone binding sites. The action of morphine on nociception and on the serotonergic system was similar to that of paracetamol; all morphine-induced effects were blocked by naloxone. These data provide further evidence for a central antinociceptive effect of paracetamol and support the hypothesis that paracetamol exerts its antinociceptive activity through the serotonergic system. Moreover, our results point to the relationship between serotonergic and opiatergic systems in the antinociceptive activity of paracetamol.     

Bright light suppresses hyperactivity induced by excitotoxic dorsal hippocampus lesions in the rat.

The hippocampus has been implicated in anxiety, novelty detection, spatial- contextual processing, and hyperactivity. Accordingly, the authors contrasted the role of the dorsal hippocampus (DH) and the basolateral amygdala complex (BLA) in an open field task that presents the onset and termination of a bright light gradient. In the dark, DH rats demonstrated impaired habituation of locomotion behavior and hyperactivity, whereas in bright light their behaviors were normal. DH rats responded differentially to the onset and termination of the light stimulus, which indicates they have normal novelty detection. BLA lesion rats responded normally to bright light. These results demonstrate that a mild fear stimulus, such as bright light, can suppress DH lesion-evoked hyperactivity, and this hyperactivity results from impaired contextual processing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dextromethorphan potentiates morphine antinociception, but does not reverse tolerance in rats

The N-methyl-D-aspartate (NMDA) and cholecystokinin (CCK)-B receptors may have a role in the development and reversal of tolerance to morphine. In morphine-tolerant rats, addition of the CCK-B receptors antagonist CI 988 or the NMDA receptor blocker dextromethorphan enhanced the antinociceptive effect of morphine on the hot plate test. However, combined administration of CI 988 and dextromethorphan did not further potentiate the antinociceptive effect of morphine in tolerant rats. Dextromethorphan by itself had no effect in tolerant rats. In drug-naive rats, dextromethorphan by itself had no antinociceptive effect, but when combined with morphine or morphine and CI 988, it significantly potentiated the magnitude and duration of the effect of morphine. Thus, unlike the reversal of tolerance with CI 988 at doses that did not potentiate the effect of morphine, the antinociception observed with the NMDA antagonist in the presence of morphine in tolerant rats may not represent the reversal of tolerance, but may instead reflect the potentiation of morphine's analgesic effect by dextromethorphan.     

Effects of amygdaloid lesions on exploration by rats

Diagnostic separation of infants with signs of cardiac failure (hypoglycemia, sepsis, myocarditis, hypoxemia) but no congenital cardiocirculatory malformation from those with a large left to right shunt is crucial in newborn management. Echocardiographic studies of 218 infants and children allowed group separation and distinction from normal by the assessment of mean velocity of circumferential fiber shortening (Vcf) and the ratio of left atrial to aortic root diameter at end-systole (LA/Ao). In normal premature and full-term infants, Vcf (1.51 +/- 0.04 [mean +/- standard error]) was significantly lower than in infants with a large shunt (2.12 +/- 0.08, P less than 0.01) and higher than in infants with nonstructural heart disease (1.18 +/- 0.06, P less than 0.001). LA/Ao ratios were comparable in the groups with a large shunt and nonstructural heart disease (1.14 +/- 0.1 and 1.26 +/- 0.2, respectively) and were significantly higher in both groups than in normal subjects (0.77 +/- 0.01, P less than 0.001). Similar echocardiographic distinctions could be made when 10 older children (aged 2 to 10 years) with cardiomyopathy were compared with 45 normal older children. Serial determination of these variables was of major assistance in patient management.     

Object-carrying by rats: Disruption by ventral mesencephalic lesions.

In 22 of 30 male Wistar rats, reliable object-carrying was elicited concurrently with self-stimulation in a shuttlebox. Unilateral electrolytic and neurotoxic 6-hydroxydopamine (6-OHDA) lesions in the vicinity of the substantia nigra in 14 of the carrier Ss disrupted object-carrying in postoperative tests. As the 6-OHDA lesions reduced ipsilateral striatal tyrosine hydroxylase levels to less than 5% of the contralateral striatum, this suggests a role for the ascending dopaminergic nigrostriatal bundle in stimulation-induced object-carrying. Shuttlebox self-stimulation was unaffected by either type of lesion, and this result is interpreted as evidence for a dissociation of the neural correlates of self-stimulation and object-carrying. Implications of this finding for S. E. Glickman and D. B. Schiff's (see record 1967-05745-001) biological theory of reinforcement are discussed. Furthermore, the ineffectiveness of substantia nigra lesions on ipsilateral hypothalamic self-stimulation implies that while the dopaminergic nigrostriatal bundle may be subserving some aspects of lateral hypothalamic self-stimulation, the role is by no means an exclusive one. (French summary) (42 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)