Simulation exercises, a problem oriented method of learning public health in medical education]

Spontaneous and amphetamine-elicited locomotor activity in rats is reduced by most clinically effective antipsychotic drugs. We have recently demonstrated that intracerebroventricular infusion of kainic acid (KA), which produces cell loss in the hippocampus and other limbic-cortical brain regions, increases spontaneous and amphetamine-elicited locomotion. The present study determined if KA lesions alter the suppressive effects of the antipsychotic drugs, haloperidol and clozapine, on spontaneous and amphetamine-elicited locomotor behavior. Young adult male rats (70 days of age) received intracerebroventricular infusions of vehicle or KA, which produced hippocampal pyramidal cell loss in each rat and more variable cell loss or gliosis in the amygdala, piriform cortex, and laterodorsal thalamus. Thirty days post-surgery, lesioned and control rats were tested once a week for locomotor responses to drug treatments. As observed previously, spontaneous locomotor activity and hyperactivity elicited by amphetamine (1.50 mg/kg s.c.) were greater in lesioned animals than controls. In addition, the level of spontaneous activity and/or amphetamine-elicited hyperlocomotion observed in lesioned rats after haloperidol treatment (0.13, 0.35, or 1.50 mg/kg s.c.) was greater than that found in controls. Locomotor responses to low (6.30 mg/kg) and moderate doses of clozapine (20 mg/kg) were similar in lesioned and control rats, although lesioned rats were more active than controls following the administration of a high dose of clozapine (30 mg/kg). These data indicate that the hyperactivity associated with limbic-cortical lesions may be insensitive to reversal by haloperidol, yet uniquely sensitive to suppression by clozapine.     

Multiple kainic acid seizures in the immature and adult brain: ictal manifestations and long-term effects on learning and memory

PURPOSE: While there is increasing evidence that the adverse effects of prolonged seizures are less pronounced in the immature than in the mature brain, there have been few investigations of the long-term effects of recurrent seizures during development. This study examined the effects of multiple administrations of the convulsant kainic acid (KA) on seizure characteristics and spatial learning as a function of brain development. METHODS: To determine the long-term effects of serial KA seizures during ontogeny, saline or convulsant doses of KA were given intraperitoneally 4 times, at 2-day intervals. Immature rats were given KA on P20, P22, P24 and P26; adult rats got KA on P60, P62, P64 and P66. Ictal characteristics and EEGs were recorded. To examine the effects of multiple KA seizures on the retention of spatial learning, water maze testing was performed before (immature group: from P16-19, adult group: from P56-P59) and after (immature: from P60-P63, adult: from P100-P103) KA injections. Finally, histology was performed to compare KA-induced damage at each age. RESULTS: In immature animals, serial KA administration resulted in seizures with a progressively longer onset latency and decreased severity. In contrast, KA serially administered to adult rats caused severe seizures after each of the 4 injections. In immature rats, epileptiform EEG changes were most prominent after the first KA injection, whereas in adults, prolonged paroxysmal EEG patterns were seen after all 4 KA injections. Before KA, both rat pups and adults acquired place learning in the water maze. One month after the final KA injection, there was no deficit in spatial learning retention in the immature group, whereas the adult group had profound impairment compared to age-matched, saline-injected controls. Histology revealed no lesions in immature rats treated multiple times with KA but profound cell loss in hippocampal fields CA4, CA3 and CA1 in rats treated serially with KA as adults. CONCLUSIONS: Previous studies have shown that a single KA injection causes prolonged status epilepticus (which persists for several hours), leading to severe histologic and behavioral sequelae in adult rats but not in pups. Our study extends those findings, demonstrating that immature rats are spared the cognitive and pathological sequelae of multiple injections of convulsant doses of KA as well.     

Effects of lesions in the basolateral amygdala on fluid intake in the rat.

Conducted 6 experiments with 33 rats with bilateral lesions in the lateral amygdaloid region and 22 intact controls. Drinking response to hypertonic saline, a cellular thirst stimulus, and to isoproterenol, probably an extracellular thirst stimulus, was normal in lesioned Ss. The overnight water intake of the lesioned Ss was a little higher than normal. However, the lesioned Ss showed a major impairment in learning to avoid ingesting a poisonous solution of LiCl when they were thirsty and an increased preference of 25% sucrose in a 2-bottle sucrose-water test. It is concluded that the basolateral region of the amygdala is involved in the effects of previous experience on drinking and not primarily in the cellular or extracellular controls of drinking. (25 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effect of hippocampal dentate granule cell lesions upon the limbic seizure model of rats

The purpose of this study was to determine the role of dentate granule cells upon limbic seizure of Wistar rat caused by unilateral intra-amygdaloid administration of kainic acid (KA). Stereotactic surgery was performed in Wistar rats and stainless steel injection chemitorode was inserted in the left amygdala. Left dentate granule cells lesion were induced by microinjection of colchicine. The rats obtained recovery period for 7 days, postoperatively. The rats were divided into two groups. One group were used for observation of symptoms and electroencephalographic findings during the limbic seizure for 6 hours after the KA injection. Another group was processed for measuring local cerebral glucose utilization (LCGU) during limbic seizure status. The histological study demonstrated a selective loss of dentate granule cells in the left hippocampus 7 days after the colchicine injection. After the KA injection, initiation of the spike discharge was significantly retarded not only in the hippocampus (from 6.01 min. to 37.25 min.) but also in the amygdala (from 2.96 min. to 10.8 min.). Progression, frequency and intensity of the KA induced seizures were also inhibited by the colchicine-induced dentate granule cells lesion. During limbic seizure status, LCGU obtained by 14C-deoxyglucose autoradiography were significantly decreased not only in the hippocampus but also in the amygdala on the site of KA injection. These data suggest that hippocampal dentate granule cells play an important role on initiation and progression of the KA induced limbic seizure. The result suggested that there was an acceleration mechanism of the limbic seizure between amygdala and hippocampus.     

Supersensitivity of anterior pituitary dopamine receptors involved in the inhibition of prolactin secretion following destruction of the medial basal hypothalamus

The medial basal hypothalamus of ovariectomized rats was destroyed using a modified Halász knife. Large increases in prolactin secretion were observed 1 and 14 days following the lesions. Long- and short-term lesioned animals were anesthetized with chloral hydrate and treated with various doses of apomorphine (0.05, 0.2, 2, 5 mg/kg). Blood samples were obtained before and 10, 30 and 60 minutes after the injection. Both the 0.05 and 0.2 mg/kg doses caused significantly greater and longer-lasting inhibition of prolactin in long-term than in short-term lesioned animals. Since the MBH was totally destroyed this study suggests that anterior pituitary dopamine receptors involved in the inhibition of prolactin secretion become supersensitive in long-term lesioned rats.     

Spiral CT: applications in the emergency patient

The influence of vasopressin (AVP) on recall of information in a passive avoidance situation after bilateral 6-OHDA lesions to the central amygdala was tested. AVP given 15 min before the retention testing at the icv dose of 1 microgram significantly prolonged avoidance latencies both in lesioned and in sham-operated rats in comparison with the respective icv saline injected animals. Insignificant increase of spontaneous locomotor activity in rats lesioned to the central amygdala was unlikely to interfere with the cognitive effect of AVP. These results suggest that dopaminergic projection to the central amygdala is not responsible for the facilitatory effect of AVP on retrieval process in a passive avoidance situation.     

Selective hippocampal lesions and behavior: Effects of kainic acid lesions on performance of place and cue tasks.

Used kainic acid (KA; 1 and 2 μg/μl) lesions to study the effects of damage to the CA3 cell field and subiculum on performance of complex place and cue tasks by 54 male albino rats. In Exp I, neuroanatomical techniques determined the selectivity of the lesions. In a within-Ss design, Ss in Exp II were trained before the operations to run on an 8-arm radial maze with procedures that involved 2 kinds of learning (place and cue) and 2 memory functions (reference memory and working memory). Interrupting the intrahippocampal circuit by damaging the CA3 cell field with KA had minimal effects on performance; injections into subiculum and complete aspiration lesions of hippocampus resulted in impairments on the place but not the cue task. Only intraventricular injections of KA affected performance on both tasks. Results fail to support either the cognitive map or the working memory theory of hippocampal function. It is suggested that distant damage beyond the immediate area of injection complicates interpretation of the results and may limit the usefulness of KA as a neurotoxin in behavioral investigations. (57 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

"Effects of Reinforcement Omission on Rats with Lesions in the Amygdala": Erratum.

Reports an error in "Effects of Reinforcement Omission on Rats with Lesions in the Amygdala" by Peter G. Henke (Journal of Comparative & Physiological Psychology, 1973[Jul], Vol 84[1], 187-193). On page 188, the sentence beginning on Line 20, Column 1 should read: "Prior to any behavioral training, six animals received bilateral RF lesions in the amygdaloid complex." (The following abstract of this article originally appeared in record 1974-06538-001.) Trained 12 male Wistar rats with bilateral lesions in the amygdala to barpress on an FI schedule of reinforcement. During test trials, when reinforcement was occasionally omitted, response rates of 12 controls increased in the subsequent interval, whereas lesioned Ss showed no significant change. In Exp II Ss received fixed-ratio reinforcement on 1 lever, which was followed by a time-out period and fixed-ratio reinforcement on a 2nd lever. Results indicate that after reinforcement was withheld Ss with damage in the amygdala did not increase responding in the subsequent time-out period, whereas controls showed significantly higher rates. Differential latencies to initiation of response after nonreinforcement were also found. The deficits following brain damage are attributed to a reduction in nonreinforcement-induced frustration. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of posttraining injection of cholinergic agonists and antagonists into the amygdala on retention of passive avoidance training in rats.

144 adult male Long-Evans rats were given a single footshock while licking a water tube and tested 24 hrs later for retention of the footshock experience. A single bilateral injection of a subseizure dose of physostigmine into the amygdala applied immediately but not 18 hrs after the footshock impaired retention. This effect appeared to be somewhat localized, as physostigmine injected into the hippocampus or lateral ventricles did not disrupt retention. Conversely, a subseizure dose of atropine sulfate into the amygdala, given immediately or 18 hrs after the footshock did not impair retention. Atropine injected concurrently with physostigmine into the same amygdaloid loci counteracted a potential physostigmine-induced retention deficit. Injection of carbachol into the amygdala also impaired retention; however, carbachol precipitated seizures and possibly exerted proactive consequences on performance. The time-dependent nature of the deficit following physostigmine is consistent with the view that injection of cholinergic agonists into the amygdala disrupts memory for the footshock experience. (36 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dissociating the anti-fear effects of septal and amygdaloid lesions using two pharmacologically validated models of rat anxiety.

Compared the effects of septal and amygdaloid lesions in 2 models of rat anxiety. Septal lesions decreased burying behavior in the shock-probe burying test and increased open-arm exploration in the elevated plus-maze test, whereas amygdaloid lesions produced neither of these anxiolytic effects. However, amygdaloid lesions increased rats' contacts of the electrified probe, an anxiolytic effect not produced by septal lesions. Each of these distinct, anxiolytic effects of septal or amygdaloid lesions were displayed together in animals with lesions of both structures. Furthermore, the magnitude of these anxiolytic effects after combined lesions were comparable to their magnitude after individual lesions. Taken together, these results suggest that the amygdala and the septum independently control the expression of different fear-related behaviors. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Altered food preferences after lesions in the basolateral region of the amygdala in the rat.

Studied the food preferences of 52 male hooded Lister and albino Wistar rats. 19 Ss were intact; 33 received bilateral lesions of the basolateral amygdala. Lesioned Ss chose different foods from controls in 10-min food-preference tests. The normal Ss ate primarily familiar chow, while the amygdala-lesioned Ss ate primarily novel foods. The lesioned Ss did not select indiscriminately but showed definite preferences. With repeated testing, the normal Ss' preferences became similar to those of the lesioned Ss. Food-preference tests in a disturbing environment suggested that the difference between the lesioned and control groups was not due to a general alteration in behavior such as fear. Other aspects of ingestive behavior, such as body weight regulation, were not primarily altered by the lesions. The basolateral amygdala may therefore be concerned with the selection of foods on the basis of previous experience. (24 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Activation of the locus coeruleus after amygdaloid kindling

PURPOSE: Substantia nigra (SN) and locus coeruleus (LC) neurons are implicated in the propagation and suppression of amygdaloid seizures. Both structures are activated concomitant with amygdaloid seizure discharges. Their mechanisms of activation, however, remain to be elucidated. SN firing is not associated with the induction of Fos immunoreactivity (ir), a marker of excitatory neuronal activation. LC has not been studied. The purpose of this investigation was to determine if amygdala-kindled generalized seizures could induce Fos-ir in the LC. METHODS: Female Sprague-Dawley rats were killed after generalized seizures induced by amygdala electrical stimulation and stained by using Fos immunocytochemistry. The number of Fos-ir neurons was compared between 15 animals with generalized seizures and four implanted, unstimulated controls. RESULTS: LC-ir neurons were significantly (p < 0.05) more prevalent after seizures than in control animals. Their numbers correlated very highly with Fos-ir in the central nucleus of the amygdala (p < 0.0001). No Fos induction was observed in LC in controls or in the SN in either group. CONCLUSIONS: Amygdala-induced generalized seizures result in Fos-ir in the LC but not in the SN. This is consistent with different mechanisms of activation possibly involving disinhibition in the SN and direct excitation in the LC.     

Decreased severity of ethanol withdrawal behaviors in kainic acid-treated rats

The involvement of kainate (KA)-sensitive regions in ethanol withdrawal behaviors was investigated in male Wistar rats given three intraperitoneal (IP) injections of KA (12 mg/kg) or saline each followed by recovery at 4 degrees C for 5 h and room temperature for 3 days and a final KA or saline injection at room temperature. Some animals received MK-801 (1 mg/kg, IP) 30 min after each injection and one group received saline only. The saline/saline, saline/MK-801, and KA/MK-801 groups displayed typical ethanol withdrawal behaviors 8-12 h after ethanol withdrawal. These behaviors were attenuated in the KA/saline group. Audiogenic seizures could be induced in all treatment groups 12 h after withdrawal. There was severe neuronal degeneration in the hippocampal CA region and the piriform cortex of the KA/saline-treated animals that was reduced by MK-801 treatment. The inferior colliculus remained intact. These results suggest that the N-methyl-D-aspartate receptor mediates KA-induced damage in limbic structures and that these regions may play an important role in typical, but not audiogenically induced ethanol-withdrawal behaviors.     

Dissociations among the anxiolytic effects of septal, hippocampal, and amygdaloid lesions.

Fear reactions of rats given bilateral lesions to the septum, hippocampus, or amygdala were compared with those of rats given sham lesions, in 2 animal models of anxiety: the shock-probe burying test and the elevated plus-maze test. Septal lesions produced anxiolytic effects in both tests (i.e., an increase in open-arm activity and a decrease in burying), whereas hippocampal and amygdaloid lesions produced neither of these effects. On the other hand, hippocampal and amygdaloid lesions impaired rats' passive avoidance of the electrified shock-probe, whereas septal lesions did not. These dissociations suggest that limbic structures such as the septum, amygdala, and hippocampus exert parallel but distinct control over different fear reactions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Post-traumatic survival and recovery of the auditory sensory cells in culture

The effects of hippocampal and lateral septum lesions were compared in rats tested in a water maze spatial memory task, and the effect of chlordiazepoxide (CDP) was examined. There was a significant interaction for lesion and CDP in the septal lesioned subjects, with the lesioned animals performing worse than control animals, and CDP improving the performance of lesioned animals. CDP had no effect on impaired performance in hippocampal lesioned animals.     

Posterodorsal amygdaloid lesions in rats: long-term effects on body weight

Bilateral lesions in the most posterodorsal aspects of the amygdala in female rats resulted in immediate and dramatic weight gains on a standard lab chow diet. The rate of weight gain returned to normal by Day 20, but the difference in body weight between animals with amygdaloid lesions and those with sham lesions was maintained for the duration of the study (60 days). Because rats with posterodorsal amygdaloid lesions have also been found to be hyperinsulinemic, it is hypothesized that the lesions result in a similar, though smaller, version of the syndrome that follows lesions of the ventromedial hypothalamus.     

Long-lasting effects of cholinergic stimulation of the amygdaloid complex in the rat.

Assigned 104 male Sprague-Dawley albino rats to 4 groups: (a) unoperated control, (b) cannulated control, (c) carbachol injections, and (d) eserine injections. Injection of carbachol into the amygdaloid complex caused EEG seizures and behavioral convulsions. After convulsions and abnormal EEG had disappeared, impaired acquisition of a 1-way active-avoidance response and facilitated acquisition of a 2-way shuttle-box avoidance response persisted. There was normal acquisition of an appetitive visual discrimination task, but no improvement in 1-way active-avoidance acquisition following daily handling that facilitated acquisition in controls. Eserine injections into the amygdala produced a deficit in 1-way avoidance acquisition similar to that produced by carbachol, without altering EEG or inducing convulsions. It is suggested that the behavioral changes were due to altered amygdaloid synaptic function which elevated the Ss' reactivity to noxious stimuli. (20 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effects of kainic acid in rats with spontaneous recurrent seizures

1. Rats with spontaneous recurrent seizures (SRS) were obtained by injection of kainic acid (KA; 10 mg/kg SC) to drug-naive rats that regularly developed wet-dog shakes followed by complex partial seizures and status epilepticus. Three to five weeks later, the rats with manifest SRS were selected. 2. The SRS rats were challenged with KA (10 mg/kg SC). The seizures induced in SRS rats by KA were similar to SRS regarding their clinical stage and duration (mean duration of seizures: 44 sec and 43 sec, respectively). The frequency of seizures was, however, increased compared with the frequency of SRS in control, vehicle-treated SRS rats (mean frequency of seizures: 12.9 and 0.4 per 3 hr, respectively). The KA-induced seizures in SRS rats differ behaviorally from KA-induced seizures in naive rats-namely, neither wet-dog shakes nor the status epilepticus could be induced. 3. Repeated injection of an equal dose of KA, applied to the SRS rats 1 day after the previous KA challenge, did not induce seizures. The loss of seizure susceptibility to KA was only temporary, as shown after a 7-day drug-free period, when the repeated injection of KA regained its seizure-triggering capacity. 4. The results indicate that reactivity to the seizure-inducing agent kainic acid changes in rats with spontaneous recurrent seizures.     

Toxoplasma lymphadenitis. Analysis of cytologic and histopathologic criteria and correlation with serologic tests

Fear reactions of rats given bilateral lesions to the septum, hippocampus, or amygdala were compared with those of rats given sham lesions, in 2 animal models of anxiety: the shock-probe burying test and the elevated plus-maze test. Septal lesions produced anxiolytic effects in both tests (i.e., an increase in open-arm activity and a decrease in burying), whereas hippocampal and amygdaloid lesions produced neither of these effects. On the other hand, hippocampal and amygdaloid lesions impaired rats' passive avoidance of the electrified shock-probe, whereas septal lesions did not. These dissociations suggest that limbic structures such as the septum, amygdala, and hippocampus exert parallel but distinct control over different fear reactions.     

Unilateral striatal grafts induce behavioral and electrophysiological asymmetry in rats with bilateral kainate lesions of the caudate nucleus.

Rats (n?=?11) with bilateral kainate lesions of the caudate nucleus and subsequent unilateral transplantation of embryonic striatal tissue into the damaged area preferred 4 months later to reach for food with the forepaw contralateral to the graft. No such asymmetry was observed in lesioned, nontransplanted (n?=?8) or unoperated (n?=?5) control rats. Good integration of the graft with the host brain was indicated by the finding that cortical spreading depression did not enter the lesioned caudate nucleus but did penetrate into the lesioned caudate with the graft almost as regularly as in intact rats. Behavioral asymmetry produced by unilateral grafts in bilaterally lesioned animals reveals the effects of transplantation with more sensitivity than the graft-induced compensation of the asymmetries caused by unilateral lesions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)