Environmental enrichment increases responding to contextual cues but decreases overall conditioned fear in the rat.

This study aimed at investigating the effects of environmental enrichment on various aspects of contextual processing in adult female rats. In experiment 1, simple conditioning was studied using either a training procedure allowing overshadowing of the contextual cues by signalling footshock with a discrete tone or a training procedure allowing a reduction of this overshadowing by explicitly unpairing the footshock and the tone. In experiment 2, contextual discrimination and contextual occasion-setting were assessed. Rats were daily exposed to two different contexts. In one context, a footshock was delivered 30s after the offset of a tone, whereas in the other context the same tone was presented alone. Experiment 3 examined familiarization to a new context. Experiment 1 showed that environmental enrichment reduced the overshadowing of contextual cues by the tone and also reduced freezing to the more predictive cue according to the training procedure used. Experiment 2 showed that environmental enrichment increased the ability of rats to discriminate two contexts. Experiment 3 showed that enriched rats familiarized faster to a new context than standard rats. Taken together, these results suggest that environmental enrichment in adult rats enhances learning about contextual cues and reduces overall fear associated with aversive events.

Electrolytic lesions of the ventral subiculum weakly alter spatial memory but potentiate amphetamine-induced locomotion.

Adult Long-Evans male rats were subjected to electrolytic lesions of the ventral subiculum, and tested for locomotor activity in the home cage, reference and working memory in the water maze, working memory in the radial maze, and D-amphetamine-induced locomotion (1mg/kg, i.p.). When compared to their sham-operated counterparts, lesioned rats showed nocturnal hyperactivity, no reference memory deficit, but working memory was impaired in the water maze and during the initial stage of radial-maze testing. Their locomotor responsiveness to D-amphetamine was exaggerated. Histological verifications confirmed lesions in the ventral subiculum. Material stained for acetylcholinesterase activity indicated septohippocampal and commissural/associational sprouting, accounting for partial damage to the perforant paths. These results showed that ventral subiculum lesions (i) do not alter the capability of rats to learn repeatedly presented spatial information, and (ii) impair, but do not prevent, spatial working memory, suggesting that the ventral subiculum is preferentially involved in short-term memory for spatial locations. Given the electrolytic nature of the lesion, the lesion-induced potentiation of the locomotor response to amphetamine is probably easier explained by partial disruption of the perforant paths than by damage to neurons of the ventral subiculum.

Grafts of fetal septal cells after cholinergic immunotoxic denervation of the hippocampus: a functional dissociation between dorsal and ventral implantation sites.

Three-month-old Long-Evans rats were subjected to intraseptal infusions of 0.8 microg of 192 IgG-saporin followed, 2 weeks later, by intrahippocampal suspension grafts containing fetal cells from the medial septum and the diagonal band of Broca. The suspensions were implanted in the dorsal or the ventral hippocampus. Sham-operated and lesion-only rats were used as controls. Between 18 and 32 weeks after grafting, all rats were tested in a water maze (using protocols placing emphasis on reference memory or on working memory) and an eight-arm radial maze. The lesion produced extensive cholinergic denervation of the hippocampus, as evidenced by reduced acetylcholinesterase-positivity and acetylcholine content. Depending upon their implantation site, the grafts restored an acetylcholinesterase-positive reinnervation pattern in either the dorsal or the ventral hippocampus. Nevertheless, the grafts failed to normalize the concentration of acetylcholine in either region. The cholinergic lesion impaired working memory performance in both the water maze and the radial maze. To a limited degree, reference memory was also altered. Grafts placed in the ventral hippocampus had no significant behavioral effect, whereas those placed in the dorsal hippocampus normalized working memory performance in the water maze. Our data show that infusion of 192 IgG-saporin into the septal region deprived the hippocampus of its cholinergic innervation and altered spatial working memory more consistently than spatial reference memory. Although the cholinergic nature of the graft-induced reinnervation remains to be established more clearly, these results further support the idea of a functional dissociation between the dorsal and the ventral hippocampus, the former being preferentially involved in spatial memory.

Effects of room and cage familiarity on locomotor activity measures in rats.

Locomotor activity measures are often used in behavioral neuroscience. There is, however, a large variability in the protocols assessing locomotor activity which may, more or less, strongly be influenced by exploration and reactivity to novelty in unfamiliar situations. Using Long-Evans male rats, we investigated how far changes, such as placing rats in a cage physically identical to the home cage supplied with fresh sawdust but kept in a familiar room, or placing the familiar home cage with the rat inside in another (unfamiliar) room, may influence the level of locomotor activity. We showed that both changes resulted in significantly increased locomotion in the first 2 h after placing the rats in the respective test situation, but there is no significant additive effect. These changes performed right before the start of the test do not alter diurnal or nocturnal locomotor activity once the first 2 h have elapsed. The results illustrate that rats kept in an environment with stable proximal features (cage, sawdust) can react by increased activity in response to more distal novelty (experimental room), and conversely, that rats in a familiar environment react to proximal changes in the home cage.

Effects of MDL 73005 on water-maze performances and locomotor activity in scopolamine-treated rats.

The stimulation of 5-HT1A receptors in the raphe or their blockade in the hippocampus can reduce cognitive deficits induced by blockade of muscarinic receptors in the hippocampus. We investigated the effects of MDL 73005 (8-[2-(2,3-dihydro-1,4-benzodioxin-2-ylmethylamino) ethyl]-8-azaspiro[4,5] decane-7,9-dione methyl sulphonate), an agonist at 5-HT1A somatodendritic autoreceptors and an antagonist at postsynaptic 5-HT1A receptors in rats treated systemically with scopolamine. Spatial memory was assessed in a water maze using protocols testing reference and working memory. Home cage locomotor activity was also determined. Working memory and locomotor activity were evaluated before and after para-chlorophenylalanine (pCPA) treatment. Scopolamine produced a weak impairment of reference memory at 0.5 mg/kg, and a more pronounced impairment of working memory at 0.25 and 0.5 mg/kg. MDL 73005 alone (2 mg/kg, i.p.) had no effect, but prevented the memory impairments induced by 0.25 mg/kg of scopolamine. Scopolamine induced hyperlocomotion. MDL 73005 alone did not affect locomotor activity, but exacerbated the hyperlocomotion induced by 0.5 mg/kg of scopolamine. pCPA did not abolish the effects of MDL 73005, suggesting that these effects were not due to an action at presynaptic receptors, or even that they involved receptors other than serotonergic ones (e.g., D2). In conclusion, MDL 73005 is able to antagonise moderate spatial memory dysfunctions induced by systemic muscarinic blockade.

Effects of the duration of progesterone treatment on the resolution of cerebral edema induced by cortical contusions in rats.

UNLABELLED: PURPOSE. The aim of the present study was to assess the effect of different durations of administration of progesterone (4 mg/kg) on the resolution of edema 6 days after medial frontal cortex contusions (MFC) in male adult rats. METHODS: Animals sustaining injury were injected with progesterone or its vehicle for 3 days or for 5 days beginning the first hour after surgery. On the 6th day the rats were killed and their brain water content was measured. RESULTS: We confirmed the presence of edema six days after MFC. However, both 3 and 5 days of treatment with progesterone significantly reduced edema in the injured brains but the five days of treatment were more effective. The effects of progesterone depend upon the duration of the treatment because there are two waves of edema. The first phase begins within a few hours of the injury and the second starts several days later. CONCLUSIONS: Our data are consistent with earlier findings showing that longer durations of progesterone administration lead to more complete behavioral recovery as well as to an increased number of surviving neurons.

8 french transradial coronary interventions: clinical outcome and late effects on the radial artery and hand function.

BACKGROUND: Limited information is available on the effects of 8 French (Fr) transradial procedures on radial patency. In addition, the effects of radial procedures and radial occlusion on hand function are unknown. METHODS: Two groups were recruited: twenty-four patients who had undergone 26 transradial 8 Fr interventions and 16 patients who had undergone 16 transradial 6 Fr procedures. At 1 year, radial patency, hand strength and hand endurance were measured. RESULTS: No major adverse cardiac events or vascular complications were noted in either group. Late radial occlusion was noted in 2/18 (11%) 8 Fr patients and 3/16 (19%) 6 Fr patients (p = ns). There were no differences in the 8 Fr group between the catheterized and uncatheterized radial arteries for diameter (3.2 +/- 1.1 mm versus 3.3 +/- 0.7 mm, respectively; p = NS) or volumetric flow (55 +/- 51 ml/minute versus 57 +/- 45 ml/minute, respectively; p = NS). No differences in hand strength or hand endurance were seen between the catheterized and uncatheterized arms in the 8 Fr group, between the 8 Fr and 6 Fr groups, or between occluded and non-occluded patients. CONCLUSION: Transradial use of 8 Fr guiding catheters appears to be feasible and safe in highly selected patients, albeit associated with a low incidence of silent radial occlusion. Additionally, neither the use of 8 Fr sheaths nor the presence of radial artery occlusion appear to adversely affect hand strength or endurance.

Selective lesions of the entorhinal cortex, the hippocampus, or the fimbria-fornix in rats: a comparison of effects on spontaneous and amphetamine-induced locomotion.

Using adult Long-Evans male rats, this experiment compared spontaneous (assessed 15 days and 4.5 months after surgery) and amphetamine-induced (assessed from 4.5 months after surgery onwards; 1 mg/kg, i.p., ten injections, 48 h apart) locomotor activity following N-methyl-D-aspartate lesions of the entorhinal cortex, electrolytic lesions of the fimbria-fornix, or ibotenate lesions of the hippocampus. Sham-operated rats were used as controls. Hippocampal and fimbria-fornix lesions, but not entorhinal-cortex lesions induced diurnal and nocturnal hyperactivity, which was attenuated over time, but only in rats with fimbria-fornix lesions. Amphetamine-induced hyperlocomotion was assessed in a familiar environment. Lesions of the entorhinal cortex potentiated the locomotor effects of amphetamine, but not lesions of the hippocampus or interruption of the axons in the fimbria-fornix pathway. Sensitization appeared to be decreased by fimbria-fornix lesions and to be prevented by hippocampal lesions. Rats with entorhinal-cortex lesions behaved as if they had already been sensitized by the lesion. These results clearly show that lesions of the fimbria-fornix, the hippocampus, and of the entorhinal cortex have different effects on spontaneous and amphetamine-induced hyperactivity, as they also have on learning and memory tasks.

Entorhinal but not hippocampal or subicular lesions disrupt latent inhibition in rats.

Latent inhibition (LI) is the deficit of conditioning resulting from repeated nonreinforced preexposure to a conditioned stimulus before its pairing with an unconditioned stimulus. There are cumulative data showing that large lesions of the hippocampal formation disrupt LI. However, the effects of selective lesions of the different components of the hippocampal formation have never been directly addressed in the same study and conditioning paradigm. The first experiment of the present study aimed at investigating the effects of excitotoxic lesions of the hippocampus, subiculum, or entorhinal cortex on LI in an "off-baseline"-conditioned emotional response procedure. Hippocampus or subiculum lesions had no effect on either LI or conditioning. In contrast, entorhinal cortex lesions disrupted LI without modifying conditioning. In Experiment 2, locomotor activity in a novel environment was assessed in the same rats. Whereas lesions of hippocampus increased locomotor activity, lesions of the subiculum or the entorhinal cortex were devoid of effect. Although both LI and habituation to novel environmental cues are thought to involve interactions between the hippocampal formation and the mesolimbic pathway, these results indicate a functional dissociation between the hippocampus and the entorhinal cortex.

Spatial memory, habituation, and reactions to spatial and nonspatial changes in rats with selective lesions of the hippocampus, the entorhinal cortex or the subiculum.

Various spatial memory deficits have been described in rats with damage to the hippocampal formation (including the subiculum and the entorhinal cortex) and particularly in rats with selective lesions of the hippocampus proper. So far, the involvement of the entorhinal cortex in spatial memory is still controversial and the role of the subiculum is poorly documented. The aim of the present study was to compare the behavioural effects of selective lesions of the hippocampus, the entorhinal cortex or the subiculum in (a) a water-maze task using testing procedures sensitive to the disruption of reference or working memory and (b) in an object exploration task designed to evaluate habituation and subsequently reactions to changes of the spatial layout of objects (spatial change) or to the substitution of a familiar object by a new one (nonspatial change). Our results showed several similarities between the behavioural consequences of damage to each of the three structures. A few differences were also noted. Hippocampal rats were impaired in all spatial tasks, but they reacted like controls to a nonspatial change. The rats sustaining lesions of the entorhinal cortex or the subiculum were not impaired in the reference-memory procedure of the water-maze task and showed a deficit in reacting to a nonspatial change. Overall, our results confirm the central role of the hippocampus in spatial memory and also suggest a role for the entorhinal cortex and the subiculum in processing spatial informations. In addition, they indicate that the entorhinal cortex and the subiculum may have a hippocampal-independent role in memory.

Fimbria-fornix vs selective hippocampal lesions in rats: effects on locomotor activity and spatial learning and memory.

The behavioral effects of interrupting the axons that pass in the fimbria and dorsal fornix were compared with the effects of selective removal of the cells that comprise the hippocampus with ibotenic acid. Starting 4.5 months after surgery, lesioned and control rats were (i) trained in both the Morris water maze and the eight-arm radial maze using protocols that placed an emphasis on either working memory (WM) or reference memory (RM) and (ii) tested for locomotor activity in the home cage. In comparison to sham-operated rats, the rats from both lesion groups were impaired in most learning/memory tasks, but there were some interesting differences between the two lesioned groups. When compared to rats with fimbria-fornix lesions (FIFX rats), hippocampal rats (HIPP rats) were slower in learning to swim to a visible platform and showed a greater impairment than FIFX rats in the radial-maze task when the testing procedure required the utilization of RM and WM in a more demanding WM task. In the test of locomotor activity, FIFX and control rats did not differ, but HIPP rats were more active than the rats in both other groups. The pattern of results obtained after a 4.5-month recovery period support the following general conclusions. (1) While there are some similarities in the effects on behavior of interrupting the axons in the fimbria-fornix compared to removing the hippocampus, there are some important differences. (2) From the findings that are available, a possible explanation to account for the difference between FIFX and HIPP rats is that the 4.5-month survival time permitted some recovery in the group of rats with FIFX lesions. (3) While it is well known that the Morris water maze and the radial-arm maze tasks provide useful measures of spatial learning and memory processes, our results suggest that the information provided by the two spatial learning tasks may differ in important respects.

Effects of enriched postoperative housing conditions on spatial memory deficits in rats with selective lesions of either the hippocampus, subiculum or entorhinal cortex.

Long-Evans male, adult rats received selective and bilateral lesions of either the hippocampus, subiculum or lateral entorhinal cortex, and were then housed for 30 days in either enriched or standard conditions. Rats were then tested in the eight-arm radial maze to assess spatial working memory and the strategies that were employed (i.e. pattern of arms visited). Lesions of the hippocampus induced both a working-memory impairment and a loss in the use of allocentric strategies to perform the task. Rats with lesions of the subiculum were also impaired but less than hippocampectomized rats and showed a similar pattern of arm visits as control rats. In contrast with other lesioned rats, rats with lateral entorhinal cortex lesions performed the task like control rats. Postoperative enriched housing conditions (EHC) globally enhanced performance of rats, but did not affect the strategies selected by the rats to solve the task. The beneficial effect of EHC was particularly obvious in rats with lesions of the subiculum. In enriched rats with such lesions, performance was not significantly different from that of control rats housed in standard conditions. The present results indicate that 1) the structures within the hippocampal formation are not similarly involved in spatial learning and memory processes and in the management of navigational demands of the radial maze, and 2) enriched conditions may enhance the spared spatial abilities of some lesioned rats thus promoting functional recovery.

Effects of postoperative housing conditions on functional recovery in rats with lesions of the hippocampus, subiculum, or entorhinal cortex.

In order to study the effects of differential housing conditions on recovery from damage to different components of the hippocampal formation, 85 rats received bilateral lesions of the hippocampus, entorhinal cortex, or subiculum or sham surgery and then were housed for 30 days in either an enriched environment or an impoverished environment. Rats were subsequently tested on a battery of tasks for assessing locomotor activity in their home cage, reactivity to novelty, spatial working and reference memory in the Morris water maze, and learning in the Hebb-Williams maze. Rats with the hippocampus removed showed impairments in most of the tasks we used (home-cage and novelty-induced locomotor activity, water maze, and Hebb-Williams maze). Most of the deficits induced by lesions to the entorhinal cortex were similar to those induced by the removal of the hippocampus. Some differences appear to be among the deficits induced by the lesions of these structures when assessing the home-cage locomotor activity, the reactions to novelty, and one aspect of the Hebb-Williams maze learning. Lesions to the subiculum induced only an impairment in the probe trial of the water-maze task. Confirming and extending previous findings in rats with various (but nonexcitotoxic) lesions of the hippocampus, an enriched environment had a beneficial effect on several of the deficits observed in the tasks we used. Further, only the rats with hippocampal lesions benefitted from having been housed in the enriched environment. However, their facilitated recovery was not observed in all tasks. After damage to different components of the hippocampal formation, the beneficial effects induced by the enriched housing conditions were shown to be both lesion-locus- and task-dependent.