Potentiating hippocampal stimulation facilitates acquisition of lever-pressing for stimulation but not food

The effect of a prior program of daily hippocampal stimulation on acquisition of lever-pressing for food, and subsequently for stimulation, was studied in 3 groups of rats—stimulated over 30 days with a single daily train (60 Hz) of potentiating stimulation (kindling), stimulated with an equal number of pulses at a non-potentiating frequency (1 Hz), and unstimulated controls. Rate of acquisition of lever-pressing for food pellets was unaffected by either stimulation pretreatment. When reinforcement was switched to hippocampal stimulation, acquisition was very slow for animals which had received no previous potentiating stimulation (1 Hz and unstimulated groups), but significantly faster for the 60 Hz animals. The results suggest that the faster acquisition of lever-pressing in kindled animals is specific to hippocampal reinforcement and that the effect is dependent on the potentiating consequences of the stimulation pretreatment.     

Kindling in the amygdala and susceptibility to stress ulcers

Kindling in the centromedial amygdala facilitated the subsequent development of restraint-induced stomach ulcers in rats. It was suggested that the neuronal hyperexcitability produced by the kindling procedure led to an increased susceptibility to gastric pathology in response to stress.     

Activation of the Locus Coeruleus After Amygdaloid Kindling

Summary: Purpose: Substnatia 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 rnechanisms of activation, however, remain to be elucidated. SN firing is not associated with the induction of Fos imrnunoreactiv-ity (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 irnmunocytochemistry. 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 disinhi-bition in the SN and direct excitation in the LC.     

Convulsions Induced by Methyl β-Carboline-3-Carboxylate in Mice: Effects of Preceding Saline Injections

The convulsant effects of a high (5 mg/kg intraperitoneally, i.p.) dose of benzodiazepine (BZD) receptor ligand methyl β-carboline-3-carboxylate (β-CCM), whether or not preceded by administration of two lower doses of β-CCM (0.5 and 1 mg/kg i.p.) or of saline were studied in nine inbred mouse strains. In five of the strains (A/J, BALB/cBy, C3H/HeJ, CBA/H, and DBA/2J), neither saline nor preceding injections of β-CCM had any effect on subsequent reactivity to the subsequent convulsant dose. In the other 4 strains, such injections induced either tolerance (CPB-K, NZB), or sensitization (C57BL/6J, XLII), whatever the compound subsequently administered (β-CCM or saline). In these strains, the data rule out any tolerance or sensitization effect due to β-CCM, but suggest that such effects could be due to injection itself.     

Kindling of the massa intermedia of the thalamus in rats

The kindling response of the massa intermedia (MI) was assessed in rats. Clinical manifestation of the MI kindling was generally similar to that of limbic kindling, and positive transfer to the amygdala (AM) was obtained following MI kindling. However, MI kindling showed (1) a relatively high afterdischarge threshold which sometimes increased during the course of kindling. (2) a seizure stage instability with frequent regression to earlier stages, (3) a failure to establish a generalized seizure triggering threshold with an ‘all-or-none’ property, and (4) a generalized tonic-clonic seizure, which was quite different from a kindledlimbic seizure, during early phase of kindling. Furthermore, the MI stimulation caused violent beating movement of the forelimbs, jumping, or running regardless of presence/absence of afterdischarge. The findings suggest that mechanisms other than a simple activation of limbic structures are involved in the process of MI kindling.     

Marked increase in anticonvulsant activity but decrease in wet-dog shake behaviour during short-term treatment of amygdala-kindled rats with valproic acid

The anticonvulsant activity of valproic acid (VPA) was determined in amygdala-kindled rats after single and repeated (total of 7 injections given 3 times per day) administration of 200 mg/kg i.p. After a single injection, VPA significantly reduced the severity and duration of the kindled seizures and increased the duration of after-discharges recorded from the stimulated amygdala, but only 12% of the animals were totally protected from seizures. The percentage of animals totally protected increased to 88% after 7 doses. This pronounced increase in the anticonvulsant activity was not related to alterations in the plasma concentrations of VPA or its major active metabolites. Furthermore, determination of VPA and its metabolites in the substantia nigra after a single and repeated administration yielded the same data, again indicating that the increase in the anticonvulsant activity was not due to drug accumulation. In contrast to the marked increase in the anticonvulsant efficacy of VPA during short-term treatment, wet-dog shake behaviour induced by a single injection of the drug was significantly attenuated after repeated dosing, indicating that the anticonvulsant effect of VPA and the wet-dog shake behaviour induced by the drug were not mediated by the same mechanism. This was substantiated by experiments with one of the major metabolites of VPA in rat plasma, trans-2-en-VPA, which had approximately the same anticonvulsant efficacy as VPA but did not induce wet-dog shakes in rats.     

The omega-3 fatty acid-derived neuroprotectin D1 limits hippocampal hyperexcitability and seizure susceptibility in kindling epileptogenesis

Purpose: Temporal lobe epilepsy, one of the most common epilepsy syndromes, is characterized by hippocampal hyperexcitability and progressive seizure susceptibility. Omega‐3 fatty acids are involved in neuronal excitability and have anticonvulsant properties. We studied the effect of docosahexaenoic acid (DHA) or its derived lipid mediator, neuroprotectin D1 (NPD1, 10R,17S‐dihydroxy‐docosa‐4Z,7Z,11E,13E,15Z,19Z‐hexaenoic acid), in evoked seizures using a rapid kindling model of temporal lobe epilepsy. Methods: DHA or NPD1 was administered in rodents with or without kindling acquisition. Locomotor seizures and evoked epileptiform hippocampal activity immediately after hippocampal stimulations were analyzed. Key Findings: DHA or NPD1 limits hippocampal electrically induced hyperexcitability. Seizures induced by kindling triggered NPD1 synthesis in the hippocampus. Supplying its precursor, DHA, or direct injection of NPD1 into the third ventricle resulted in attenuation of kindling progression and hippocampal hyperexcitability. Significance: The significance of NPD1 in temporal lobe epilepsy could open new pathways for understanding the initiation and propagation of seizures and the role this lipid mediator plays in the neuronal network.