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GABA, g-aminobutyric acid; IP, intraperitoneally; IV, intravenously; N/A, information not available; PN, postnatal day; sub-Q, subcutaneously. "See the text for additional information about the correlation of convulsant drug doses and elicited seizure types. Doses for younger ages are available in the text.

GABA, g-aminobutyric acid; IP, intraperitoneally; IV, intravenously; N/A, information not available; PN, postnatal day; sub-Q, subcutaneously. "See the text for additional information about the correlation of convulsant drug doses and elicited seizure types. Doses for younger ages are available in the text.

Neuropathology is usually negligible. These drugs are commonly used to produce acute seizures without long-term survival. Although high doses may lead to prolonged tonic-clonic seizures, adult animals usually die during these seizures. Minor changes in the cerebellum have been described after convulsions induced by pentylenetetrazol and bicuculline (Ben-Ari et al., 1981b). In adult rats, induction of SE as a prerequisite for occurrence of neuropathology changes is difficult when using these drugs. However, in immature rats it is possible to sustain SE using repeated administrations of subconvulsive doses (Nehlig and de Vasconselos, 1996; Pereira de Vasconcelos et al., 1995). Resulting neuronal injury is only transient and does not lead to neuronal death (Pineau et al., 1999).

Relationship to Human Seizure Disorders

Differential features of seizures induced by GABA-related substances can be related to different seizures in humans (Engel, 2001). Thus motionless stare accompanied by rhythmic EEG spindles, which involves thalamocortical circuits, is considered a model of generalized seizures— typical absence seizures (Depaulis et al., 1989). Clonic seizures are considered a model of generalized seizures— myoclonic seizures (Loscher and Schmidt, 1988). Finally, tonic-clonic seizures are believed to represent generalized seizures—tonic-clonic seizures (Sarkisian, 2001).

Pentylenetetrazol

Methods of Generation

Originally a cardiostimulant, pentylenetetrazol (Cardia-zol, Leptazol, Metrazol, pentamethylenetetrazol, pentetra-zol, pentazol), or PTZ, has significant convulsant potency in mice, rats, monkeys, and humans (Reinhard and Reinhard, 1977; Swinyard et al., 1989; Vernadakis and Woodbury, 1969a, b). PTZ-induced clonic seizures represent a routine test for screening anticonvulsants (Swinyard et al., 1989). PTZ freely dissolves in saline or water and can be administered sub-Q, IP (most commonly), or IV (less commonly, usually via the tail vein). Repeated low doses of PTZ administered IP may be used to induce SE in immature rats (Nehlig and de Vasconselos, 1996; Pereira de Vasconcelos et al., 1995). Developmental CD50 levels for clonic and tonic-clonic seizures in male Wistar rats are shown in Figure 2 (according to (Velisek et al., 1992). CD50 levels for IP and IV administration are lower compared with those of sub-Q doses (Fisher, 1989). For practical purposes, doses around 100mg/kg IP or sub-Q are usually used. With these doses, seizures develop within 20 minutes after application.

Defining Features

PTZ induces all four behavioral phenomena: freezing, myclonic twitches, clonic seizures, and tonic-clonic sei-

FIGURE 2 CD50 for clonic and tonic-clonic seizures induced by the subcutaneous administration of pentylenetetrazol (PTZ) during postnatal development of Wistar rats (according to Velisek et al., 1992). Mean (M) ± standard error of the mean (SEM) (in mg/kg) are displayed. Clonic seizures were regularly induced by PTZ from the third postnatal week; tonic-clonic seizures occurred throughout development.

FIGURE 2 CD50 for clonic and tonic-clonic seizures induced by the subcutaneous administration of pentylenetetrazol (PTZ) during postnatal development of Wistar rats (according to Velisek et al., 1992). Mean (M) ± standard error of the mean (SEM) (in mg/kg) are displayed. Clonic seizures were regularly induced by PTZ from the third postnatal week; tonic-clonic seizures occurred throughout development.

Adult rat, 5 min after PTZ 40 mg/kg i.p.

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