This unit describes a protocol to perform chemical kindling in mice. Kindling is a chronic animal model of epilepsy that has been extensively studied to understand the process of epileptogenesis and discover novel anti-epileptic compounds. Kindling is a phenomenon where a sub-convulsive stimulus (either chemical or electrical), if applied repetitively and intermittently, will ultimately lead to the generation of full-blown convulsions. Kindling can be induced either by (1) electrical stimulation of different brain regions (electrical kindling) or (2) using various chemical agents (chemical kindling). This unit discusses in detail the methodology to execute pentylenetetrazol (PTZ; a GABA(A) receptor antagonist)-induced chemical kindling in mice. PTZ is administered chronically at a sub-convulsive dose for a number of days. Seizure score is calculated after each PTZ injection. The effect of test/reference compounds can be tested by administering them either prior to the initiation of kindling (pre-kindling phase) or after animals are fully kindled (post-kindling phase).

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Berberine, an isoquinoline alkaloid of the protoberberine type found in an array of plants, has been used in Indian and Chinese medicines as an antimicrobial, stomachic, bitter tonic and in the treatment of oriental sores. Although pharmacological investigations of berberine have been reported by many in the past, there is renewed interest in berberine because of its reported beneficial effect in various neurodegenerative and neuropsychiatric disorders. The alkaloid is reported to modulate neurotransmitters and their receptor systems in the brain. This review attempts to discuss the pharmacological basis of the use of berberine in various central nervous system and related disorders. Its protective effect in Alzheimer's, cerebral ischemia, mental depression, schizophrenia and anxiety are highlighted. However, more detailed clinical trials along with a safety assessment of berberine are warranted for positioning the alkaloid in the treatment of neurological disorders.

Tetramethylenedisulfotetramine (tetramine; TETS) is a potent convulsant poison that is considered to be a chemical threat agent. To provide a basis for the investigation of antidotes for TETS-induced seizures, we characterized the convulsant activity of TETS in mice and rats when administered by the intraperitoneal, intravenous, oral, and intraventricular routes as a single acute dose and with repeated sublethal doses. In mice, parenteral and oral TETS caused immobility, myoclonic body jerks, clonic seizures of the forelimbs and/or hindlimbs, tonic seizures, and death. The CD 50 values for clonic and tonic seizures after oral administration were 0.11 and 0.22 mg/kg, respectively. Intraventricular administration of TETS (5-100 g) in rats also caused clonic-tonic seizures and death. In mice, repeated sublethal doses of TETS at intervals of 2, 24, and 48 h failed to result in the development of persistent enhanced seizure responsivity ("kindling") as was observed with repeated pentylenetetrazol treatment. In mice, sublethal doses of TETS that produced clonic seizures did not cause observable structural brain damage as assessed with routine histology and Fluoro-Jade B staining 7 days after treatment. However, 1 to 3 days after a single convulsant dose of TETS the expression of glial fibrillary acidic protein, an astrocyte marker, and ionized calcium binding adaptor molecule 1, a microglia marker, were markedly increased in cortex and hippocampus. Although TETS doses that are compatible with survival are not associated with overt evidence of cellular injury or neurodegeneration, there is transient reactive astrocytosis and microglial activation, indicating that brain inflammatory responses are provoked.

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