The effect of amygdala-kindled seizures on the acquisition of taste and odor aversions

Two experiments were conducted to investigate the effect of amygdala-kindled seizures on the acquisition of fluid aversions using taste, odor, and compound taste-odor cues. In Experiment 1 all subjects were poisoned with lithium chloride 30 minutes after ingesting a novel taste. Experimental subjects were either kindled 15 minutes following ingestion or 15 minutes following LiCl injection. The strength of the taste aversion in the kindled animals was significantly attenuated compared to nonkindled controls. There was a tendency for kindling within the CS-US interval to be more disruptive than kindling that occurred after LiCl injection. The second study explored the effect of kindling after the CS on the development of aversions to an odor cue or a compound taste-odor cue. This study found that kindling after drinking effectively blocked the acquisition of both odor and taste aversions and compounding did not affect the strength of the odor aversion.     

杏仁核点燃鼠海马不同亚区Bax mRNA的表达

目的:观察细胞凋亡调控基因Bax mRNA在癫癎鼠海马不同亚区的表达。方法:利用电极植入鼠脑杏仁核的方法建立点燃癫癎模型,采用原位杂交法检测鼠脑海马CA1、CA2、CA3及齿状回(DGL)区Bax mRNA的表达。结果:正常大鼠海马各区少见Bax mRNA阳性细胞表达,杏仁核植入电极大鼠及其点燃后海马各区Bax mRNA表达阳性细胞数增多,点燃鼠Bax mRNA阳性细胞平均光密度高于仅仅植入电极鼠,海马不同亚区Bax mRNA阳性细胞平均光密度值不同。结论:杏仁核点燃癫癎模型鼠的海马不同亚区均存在Bax mRNA表达增强,但不同亚区对Bax mRNA表达敏感性不同,以DGL区为最高。     

Absence seizures during pregnancy in WAG/Rij rats

Spontaneously occurring spike-wave discharges (SWDs) and serum concentrations of ovarian steroid hormones were investigated before, during and after pregnancy in WAG/Rij rats, a rat strain with genetically determined absence seizures. Eight groups of rats were included in the assays of progesterone and estradiol: rats at diestrus, at various days of pregnancy and at lactating days. The number of SWDs in cortical EEG of WAG/Rij rats was decreased from the 3rd up to the 18th day of pregnancy and subsequently increased to control level. Thereafter, a new decrease was found 2-3 days after parturition. Serum concentration of progesterone was threefold increased at the 3rd day of pregnancy, remained elevated until the 18th day of pregnancy and returned to control values before delivery. Over measured days, estradiol was significantly elevated only at the 18th day of pregnancy. Results demonstrate that physiological conditions induced by the state of pregnancy lead to suppression of occurrence of SWDs. Changes in plasma progesterone concentration correspond to the changes in number of SWDs: an increased level of progesterone during pregnancy is accompanied by a decreased number of SWDs, while a decrease in circulating progesterone before parturition is paralleled by an increase of SWDs. Of interest, the relationship between SWDs and concentration of progesterone found during pregnancy is diametrically opposite to results obtained in acute administration studies of progesterone in nonpregnant animals.     

The protective effect of dl-tetrahydropalmatine against the development of amygdala kindling seizures in rats

The influence of dl-tetrahydropalmatine (THP), an active component isolated from a Chinese herbal medicine corydalis, was tested on the development of electrically kindled amygdala. The seizure activity was quantified by a ultrasonic system for vertical motion measurements. Intraperitoneal injection of THP (20 or 30 mg kg⁻¹) 30 min before applying the daily kindling stimulus prevented the development of the kindling process. The behavioral seizure score and the motion responses which normally develop during electrical kindling were reduced below their initial values. The results suggest that THP is a very effective antiepileptogenic and anticonvulsant agent when applied to electrically kindled rats.     

Event-related potentials in complex partial seizures

Summary Both early (N1 and P2) and late (N2 and P3) event-related potentials (ERP) were obtained in 16 patients with complex partial seizures, 12 with left hemispheric ictal focus and 4 with right, to see if they help in lateralizing the seizure focus, and also to determine if they correlate with behavioral (MMPI, Bear-Fedio), attentional (Trails A and B), cognitive (WAIS-R, Boston Naming, Warrington Word and Face recognition) and mental speed (Stroop color naming and reading) tasks. Early waves were more often lateralized than late waves but both were often falsely lateralizing. Early waves were better correlated with behavioral tasks whereas late waves were better with those measuring mental speed, attention and cognition. These data tentatively discourage the utility of ERP in preoperative lateralization of seizure focus but argue for their potential value in psychophysiological correlations.We thank United Way of Michigan for supporting this study.Thanks are due to David Rix, R. EEG T. and Shirley Browning, EEG T. for technical help and Venkat Posina Rayudu, B. Tech. for statistical help.     

Effects of gestational allopregnanolone administration in rats bred for high affective behavior

The anxiolytic neurosteroid allopregnanolone (3α-hydroxy-5α-pregnan-20-one or 3α,5α-THP) has been proposed to play a developmental role in emergent neural regulation of affective behavior. This experiment examined whether allopregnanolone administered during the last week of gestation in rats would alter neonatal and adult offspring behaviors in the selectively-bred High vocalizing line, who have low levels of allopregnanolone and high levels of anxious/depressive behaviors. Dams were injected twice a day with the neurosteroid or vehicle, or handled as controls, and were tested on the elevated plus maze just before parturition. Maternal behavior was assessed throughout the first week of life, and affective behavior in the offspring was tested at one week of age (ultrasonic vocalizations test) and as adults (plus maze and forced swim tests). Offspring prenatally exposed to allopregnanolone were less anxious as neonates and less depressed as adults compared to both control groups. Only male adult offspring, however, revealed less anxious behavior on the plus maze. Neither the dams' anxiety behavior measured in late gestation nor their postnatal maternal behavior was altered compared to controls, suggesting a direct, long-lasting effect of gestational allopregnanolone on the developing fetal brain independent of mediating maternal factors. These results are discussed in light of new evidence about the developmental role of the GABA-A receptor prenatally.     

Serotonin receptor binding and mRNA expression in the hippocampus of fearful amygdala-kindled rats

Amygdala kindling in rats increases fear behavior. The neural correlates of this fear are not well understood. In this experiment, we investigated the relation between serotonin receptor binding and mRNA expression and fearful behavior in amygdala-kindled rats. Rats received either 100 kindling stimulations or sham stimulations, and their fear behavior was subsequently assessed in an unfamiliar open field. Then, the rats were sacrificed and 5-HT transporter binding, 5-HT1A and 5-HT2A receptor binding, and 5-HT1A mRNA expression in several brain regions was assessed. The kindled rats were significantly more fearful in the open field than the sham-stimulated rats. They also had significantly more 5-HT1A receptor binding and mRNA expression in the dentate gyrus than the sham-simulated rats, and these increases in 5-HT1A receptor binding and mRNA expression were significantly correlated to the increases in fear. There were no significant differences between the kindled and sham-stimulated rats in 5-HT transporter binding or 5-HT2A receptor binding. These results suggest that alterations in 5-HT1A receptors in the dentate gyrus may play a role in the expression of kindled fear.     

Withdrawal effects from progesterone and estradiol relate to individual risk-taking and explorative behavior in female rats

Withdrawal from progesterone and estradiol has been used as an animal model of premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD). In the clinical population individual sensitivity to sex steroid hormones, personality and heredity influence PMS/PMDD. Understanding the phenotypic risk factors of PMS/PMDD and drug development requires an animal model which incorporates individual steroid sensitivity. The main objective of this study was to investigate whether the individual trait of risk-taking and exploration influence the severity of PEWD in female rats. Thirty-two female Wistar rats in their diestrus phase were tested in the open field (OF) and divided into high responders (HR) and low responders (LR). Injections were given i.p. twice daily for 6 days, either 5 mg/kg progesterone combined with 10 µg/kg 17β-estradiol, or vehicle (sesame oil). After a 24-hour withdrawal the animals were tested in the elevated plus maze (EPM). Blood samples for CORT analysis were collected after both behavioral tests. The HR rats withdrawn from progesterone and estradiol, spent less time on the EPM open arms and had lower CORT levels than the HR controls. The LR group showed no differences in EPM behavior and CORT levels during PEWD. The controls showed a stable trait of risk-taking and exploration, indicated by behavioral and CORT level correlations between the OF and EPM tests. These findings show that female rats with the trait of risk-taking and explorative behavior (HR) are more affected by PEWD.     

Absence seizures are reduced by the enhancement of GABA-ergic inhibition in the hippocampus in WAG/Rij rats

Classical theories on absence epilepsy suggest that spike-wave discharge (SWDs) represent thalamo-cortical oscillations, where an abnormally excitable cortex interacts with thalamus and brain stem reticular formation. The limbic system is generally not included in any theory about the pathogenesis of absence seizures. However, some data demonstrated that the alterations in the limbic system attribute to the expression of absence epileptic phenotype in genetic models of absence epilepsy. The present study investigated whether local intrahippocampal administration of progesterone (a GABA_A-mimetic) and tiagabine (an inhibitor of GABA (re)uptake) might affect the occurrence of SWDs. Male WAG/Rij rats were implanted with permanent electroencephalograph (EEG) electrodes and bilateral cannulas in the CA1-CA3 region of the dorsal hippocampus. Control rats had bilateral cannulas in the cortical area above the hippocampus. Rats received intracerebral injections of progesterone (5 mg/ml), 45% β-cyclodextrin (CD), saline, or tiagabine (2 mg/ml). EEG recordings were made before and after injection. Progesterone, CD, and tiagabine administration to the hippocampus reduced SWDs for 60 min following administration without behavioral or electroencephalographic side-effects. Both progesterone administration into the cortex and saline injection into the hippocampus yielded no changes in the occurrence of SWDs. These data suggest that activation of GABA-ergic transmission in the hippocampus has an inhibitory effect on cortico-thalamo-cortical circuits underlying the generation of SWDs and might be critically involved in the regulation of absence seizures.     

The benzodiazepine partial inverse agonist Ro15-4513 alters anticonvulsant and lethal effects of carbamazepine in amygdala-kindled rats

Prenatal malnutrition-induced fetal growth retardation in the rat results in elevated arterial blood pressure at adulthood. To test the contribution of cardiovascular sensory C fibers in the hypertensive state, arterial blood pressure was measured in prenatally undernourished rats treated at birth with capsaicin. The effects of the neonatal capsaicin treatment on heart rate and respiratory frequency were also evaluated. Maternal malnutrition resulted in body and brain weights deficits in the offspring that were not modified by neonatal capsaicin treatment. Capsaicin treatment did not change the cardiovascular parameters in normal rats, but prevented the elevation of arterial blood pressure and heart rate in malnourished animals. These results indicate that elevation of arterial blood pressure in prenatally malnourished rats depends on the activity of some sensory unmyelinated C fibers.     

Anticonvulsant and antiarrhythmic effects of nifedipine in rats prone to audiogenic seizures

Calcium ion participates in the regulation of neural transmission and the presynaptic release of neurotransmitters. It is also involved in epileptic events, cardiac arrhythmias and abnormal conduction of stimuli. The purpose of the present study was to evaluate the effects of nifedipine, a calcium channel blocker, on epileptic seizures and on reperfusion arrhythmias in rats prone to audiogenic epileptic seizures (Wistar audiogenic rats, WAR) and in normal Wistar rats (N = 6/group). The seizure severity index was applied after an intraperitoneal injection of 20 or 40 mg/kg nifedipine (N20 and N40 groups, respectively). The Langendorff technique was used to analyze cardiac function, as well as the incidence and severity of the reperfusion arrhythmias after ligature and release of the left coronary artery in rats treated or not with nifedipine. We found that nifedipine treatment decreased seizure severity (0.94 ± 0.02 for WAR; 0.70 ± 0.10 for WAR + N20; 0.47 ± 0.08 for WAR + N40) and increased the latent period (13 ± 2 s for WAR; 35 ± 10 s for WAR + N20; 48 ± 7 s for WAR + N40) for the development of seizures in WAR. Furthermore, the incidence and severity of the reperfusion arrhythmias were lower in WAR and normal Wistar rats injected with nifedipine. In WAR, these effects were mediated, at least in part, by a decrease in heart rate. Thus, our results indicate that nifedipine may be considered to be a potential adjuvant drug for epilepsy treatment, especially in those cases associated with cardiac rhythm abnormalities.     

Mediodorsal thalamic stimulation is not protective against seizures induced by amygdaloid kindling in rats

Deep brain stimulation (DBS) is now emerging as a new option for treating intractable epilepsy. Cumulative studies suggest that the mediodorsal thalamic nucleus (MD) is involved in limbic seizure activity. This study aims to investigate whether DBS of the MD can protect against seizures induced by amygdaloid kindling. We studied the effect of low-frequency stimulation (LFS, 1 Hz) or high-frequency stimulation (HFS, 100 Hz) in the MD on amygdaloid kindling seizures. During the kindling acquisition, DBS in the MD was daily administered immediately after the kindling stimulus or before the kindling stimulus (preemptive DBS). The effects of both post-treatment of DBS and preemptive DBS in the MD on the expression of amygdaloid kindling seizures were evaluated. We found the DBS or preemptive DBS in the MD, either LFS or HFS, did not significantly change the rate of amygdaloid kindling. Similarly, DBS or preemptive DBS in the MD did not significantly change any parameters representing the expression of amygdaloid kindling. Our study suggests that DBS in the MD may have no significant effect on limbic seizures.     

Histories of depression, allopregnanolone responses to stress, and premenstrual symptoms in women

Twenty-six women meeting DSM criteria for premenstrual dysphoric disorder (PMDD) and 39 non-PMDD controls were tested for allopregnanolone (ALLO) responses to mental stress. Approximately half of each group had a history of depression (DEP) (14 PMDD, 17 non-PMDD), though all were free of current psychiatric illness. ALLO was sampled in response to venipuncture stress, after an extended baseline, and again 30 and 60 min following the onset of mental stressors. All women with prior DEP, regardless of PMDD status, showed a blunted ALLO stress response at 30 and 60 min (p < 0.05), and also failed to show the expected decrease from venipuncture to baseline rest (p = 0.08) compared to women with no prior DEP. Women with prior DEP did not show the expected correlation between progesterone and ALLO (r = 0.16) that was seen in those with no prior DEP (r = 0.37, p < 0.05). ALLO levels at extended baseline and blunted ALLO reactivity predicted more severe premenstrual symptoms, but only in PMDD women with prior DEP (p values <0.05). These results suggest that a history of DEP is associated with a failure of ALLO to be appropriately responsive to challenge, with alterations in the conversion of progesterone to ALLO, and confirm prior reports linking ALLO to symptoms in PMDD, but only in PMDD women with histories of DEP.     

Effect of oleamide on pentylenetetrazole-induced seizures in rats

Oleamide exhibits antiepileptic activity and significantly decreases the degree of pentylenetetrazole-induced seizures. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 2, pp. 185–187, February, 2008     

柴胡皂苷a对难治性癫痫大鼠痫性发作的影响

目的探讨柴胡皂苷a（SSa）对匹罗卡品致难治性癫痫模型大鼠痫性发作的影响。方法将制备成功的48只SD难治性癫痫大鼠模型随机分为模型组（B）、丙戊酸钠组（C）、柴胡皂苷a低剂量组（D）和高剂量组（E）4组,每组各12只,另有空白对照组（A）12只。A、B组给予等量生理盐水,C组用量为200mg/kg,D、E组用药浓度依次为1.09mg/kg、2.18mg/kg,A、B、C组灌胃给药,D、E组腹腔注射给药。分别观察给药4周、8周后痫性发作次数、平均发作时间及发作级别的变化。结果痫性发作方面,A组无痫性发作,B组大鼠痫性发作明显（P〉0.05）,C、D、E组大鼠痫性发作均有不同程度的减轻（P〈0.05）,E组大鼠痫性发作减轻最明显。结论柴胡皂苷a能减轻难治性癫痫大鼠的痫性发作,有明显的抗癫痫作用。     

Absence of modifications in gamma-aminobutyric acid metabolism after repeated generalized seizures in amygdala-kindled rats

Alterations in gamma-aminobutyric acid (GABA) metabolism have been investigated in the kindling model of epilepsy. Numerous generalized seizures were induced by amygdala-kindling stimulations in rats. One week after the last stimulation, there were no changes in GABA levels nor in the activity of enzymes responsible for the synthesis (glutamic acid decarboxylase) and catabolism (GABA transaminase and succinyl semialdehyde dehydrogenase). These results do not exclude other changes in GABA function as modifications of transport or receptors.     

A genetic,physiological, and biochemical investigation of audiogenic seizures in rats

Two kinds of audiogenic seizures are characteristic of the KM rat strain, selected by Krushinsky and Molodkina in Moscow in the 1940s. This strain is now approximately 100% sound sensitive. Diallel crosses have demonstrated the polygenic nature of this behavior, with most alleles for seizures being recessive. Myoclonic seizures which develop after several sound exposures are a special form of kindling, involving the limbic system. Selection for low and high rates of myoclonic seizures was successful. Several unique, physiological features of the audiogenic seizures in this rat strain are described, as well as data on RNA and protein synthesis inhibition effects on seizure formation.     

Behavioral insensitivity to progesterone during lactation in female rats

Lactating female rats failed to display sexual receptivity after receiving 50 μg of estradiol benzoate followed by 1 mg of progesterone. Lactating rats appear to be insensitive to progesterone, based on several experiments. In ovariectomized control rats receiving moderate estrogen priming (1 μg EB for 3 days), progesterone greatly facilitated sexual receptivity; similarly estrogen-primed lactating females showed no responsiveness to progesterone injections, even at a high dose of progesterone (10 mg). Consistent with this reduced behavioral responsiveness to progesterone, lactating females had significantly reduced nuclear progestin receptor levels after an injection of 1 mg progesterone compared to ovariectomized controls. On the other hand, both ovariectomized controls and lactating rats responded with high levels of receptivity to 3 days of priming with 10 μg of estradiol benzoate (without progesterone). Lactating females treated for 3 days with a moderate dose (1 μg) of estradiol benzoate showed slightly reduced receptivity compared to ovariectomized controls; this result could reflect a reduced sensitivity to estrogen but is more likely related to the somewhat lower serum levels of estradiol and consequently lower nuclear estrogen receptors in lactating females compared to ovariectomized controls. The possibility of reduced sensitivity to estrogen leading to a reduced sensitivity to progesterone cannot be eliminated (since animals respond to progesterone only after estrogen priming); however, the reported results favor the idea that lactating females are primarily refractory to progesterone and do not have a generalized insensitivity to estrogen.     

Relationship between amnesia and brain seizures in rats

The brain stimulation intensity necessary to produce seizures and retrograde amnesia was examined at three locations: frontal cortex, posterior cortex, and a far posterior placement. Posterior cortex had the lowest brain seizure and retrograde amnesia thresholds; the far posterior placement had the highest brain seizure and retrograde amnesia thresholds. These results suggest that the amnesic properties of the brain stimulation may be linked in some way to brain seizures. However, the relationship is not a simple one; cortically elicited brain seizures are not always effective in disrupting memory.