The Pontine Reticular Formation Is a Requisite Nucleus in the Neuronal Network Mediating Clonic Audiogenic Seizures: Focal Microinjection Studies.
Abstract number :
2.022
Submission category :
Year :
2001
Submission ID :
317
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
M. Raisinghani, Pharmacology, Southern Illinois Univ Sch Med, Springfield, IL; C.L. Faingold, Ph.D., Pharmacology, Southern Illinois Univ Sch Med, Springfield, IL
RATIONALE: Audiogenic seizures (AGS) are a common form of convulsive seizures in rodents, and these seizures can be induced, for example during ethanol withdrawal, and they can be inherited. AGS are also seen in the genetically epilepsy-prone rats (GEPRs) in both substrains. GEPR-3s exhibit AGS characterized by wild running and running and bouncing clonus; and GEPR-9s exhibit wild running followed by tonic convulsions. Recent evidence suggests that the caudal pontine reticular formation (cPRF) is critical for the tonic convulsions in GEPR-9s, but it is not clear if the cPRF participates in the neuronal network subserving the clonic seizures of GEPR-3s. Excitatory amino acid (EAA) receptors play a key role in modulation of seizures, including AGS. However, the role of EAA receptors in the cPRF has not been explored in GEPR-3s.
METHODS: Cannula guide tubes were stereotaxically implanted chronically in GEPR-3s over the cPRF under ketamine/xylazine (85/3 mg/kg) anesthesia. At least 7 days later, bilateral focal microinjections of an NMDA receptor antagonist, 2-amino-7-phosphonoheptanoate (AP7), were administered at a rate of 0.25 [mu]l/min/side via inserted cannulae. AGS were evoked by presentation of an electrical bell (122 dB SPL) given until the onset of AGS or for a maximum of 60 sec.
RESULTS: AP7 (12.5 nmol/side) completely blocked all components of AGS at 30 min post-infusion, although the animals continued to display startle responses at the onset of the acoustic stimulus. Mild ataxia was often observed immediately after the microinfusion, and increased motor behavior was also observed from 40 min to 2 hr after drug infusion. An increase in escape behavior was also observed immediately after and up to 4 hr post-infusion. Seizure scores returned to pre-infusion level by 120 hr after the microinjection. Saline microinjections were without effect on AGS or spontaneous behavior.
CONCLUSIONS: The complete inhibition of seizures after blockade of NMDA receptors in cPRF indicates that EAA receptors play a vital role in modulating the seizure activity in this structure. It also shows that cPRF is a requisite structure in the neuronal network for AGS in GEPR-3s, playing a critical role in propagation of seizures, as shown previously in GEPR-9s and in ethanol withdrawal.
Support: NIH NIAAA AA11628