Brain norepinephrine and convulsions in the genetically epilepsy-prone rat: sex-dependent responses to Ro 4-1284 treatment.

Abstract

Seizure predisposition in the Genetically Epilepsy-Prone Rat (GEPR) is at least partially dependent on central nervous system noradrenergic deficits. We have previously shown that moderate seizure GEPRs (GEPR-3) experience an increase in seizure severity after receiving Ro 4-1284, a monoamine vesicle inactivating drug. We are now reporting the effect of this drug on severe seizure GEPRs (GEPR-9). Motives for this study were: (a) to determine the effects of further depletion of innately deficient monoaminergic stores on seizure latencies and (b) to investigate whether a previously documented seizure severity difference between the sexes is related to the defective monoaminergic system in these subjects. GEPR-9s with known seizure history were tested for latency to onset of running phase and convulsion 45 minutes after Ro 4-1284 or saline administration. Brain norepinephrine levels were also determined. Ro 4-1284 caused severe depletion of monoamines in all brain areas assayed in both sexes of GEPR-9s and also caused a reduction in the latencies for onset of running and convulsion. The drug-induced norepinephrine depletion across the brain areas surveyed was significantly greater in females than in their male littermates. These observations prompt us to postulate that noradrenergic neurons in female GEPR-9s are functionally different from those in males and that this difference is detected in the differential effectiveness of Ro 4-1284 between the two sexes. Also, the influence of gonadal hormones on seizure predisposition and on the neurochemical actions of Ro 4-1284 may be different in GEPR-9 males and females.

• Authors: P K Mishra, J W Dailey, C E Reigel, P C Jobe
• Journal: Life sciences (Life Sci) Vol. 42 Issue 11 Pg. 1131-7 ( 1988) ISSN: 0024-3205 [Print] Netherlands
• PMID: 3347143 (Publication Type: Journal Article)

Chemical References

• Quinolizines
• 2H-Benzo(a)quinolizin-2-ol, 2-Ethyl-1,3,4,6,7,11b-hexahydro-3-isobutyl-9,10-dimethoxy-
• Norepinephrine

Topics

• 2H-Benzo(a)quinolizin-2-ol, 2-Ethyl-1,3,4,6,7,11b-hexahydro-3-isobutyl-9,10-dimethoxy- (pharmacology)
• Acoustic Stimulation
• Analysis of Variance
• Animals
• Brain (drug effects, metabolism)
• Epilepsy (genetics)
• Female
• Male
• Norepinephrine (metabolism)
• Quinolizines (pharmacology)
• Seizures (metabolism)
• Sex Characteristics