The proconvulsant effect of nigral infusions of THIP on flurothyl-induced seizures in rat pups

Xu, S.G.; Garant, Douglas S.; Sperber, Ellen F.; Moshé, Solomon L.

doi:10.1016/0165-3806(92)90070-d

Cited by 19 publications

(12 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When these agonists were injected into the immature SNR, however, no anticonvulsant effects was apparent observed at any dose: all that was apparent were the proconvulsant effects we reported previously (8,16). A similar trend was observed with the structurally unrelated GABAA agonist THIP, although the effects of the high doses did not reach a statistically significant level.…”

Section: Discussionsupporting

confidence: 65%

“…These data, and similar findings in rat pups (8,15), argue against the possibility that a proconvulsant effect of high doses of muscimol or THIP is due to spread of drug from SNR to adjacent structures. Some data were previously reported: muscimol 12.5-200 ng in adults (13) and 25-200 ng in pups (8) and THlP in pups (16). I), we cannot rule out the possibility that a proconvulsant effect of high agonists doses dose, ng/SN ceptor antagonist.…”

Section: Discussionmentioning

confidence: 70%

“…Finally, because intranigral microinjections of 50-700 ng THIP in rat pups cause a dose-dependent exacerbation of seizures similar to that reported for muscimol (16), we determined whether THIP (25&1,400 ng) might also have both anti-and proconvulsant effects in the adult SNR. We first tested the hypothesis that lower (6.25 ng) or higher (400-1,600 ng) doses of intranigral muscimol in adults might produce proconvulsant effects similar to those observed in pups.…”

Section: Discussionmentioning

confidence: 89%

“…This antagonist-like effect is not unique to muscimol: Injections of THIP (4,5,6,7-tetrahydroisoxazolo- [ 5,4-c]pyridin-3-01), another GABA, receptor agonist (15), are also proconvulsant in 16day-old rats (16). This antagonist-like effect is not unique to muscimol: Injections of THIP (4,5,6,7-tetrahydroisoxazolo- [ 5,4-c]pyridin-3-01), another GABA, receptor agonist (15), are also proconvulsant in 16day-old rats (16).…”

Section: Discussionmentioning

confidence: 99%

“…In sharp contrast, the same doses of intranigral muscimol that are anticonvulsant in adult rats produce a dose-dependent facilitation of flurothyl seizures when microinjected into the SNR of 16-dayold rat pups (8), a proconvulsant action similar to that of BIC. This antagonist-like effect is not unique to muscimol: Injections of THIP (4,5,6,7-tetrahydroisoxazolo- [ 5,4-c]pyridin-3-01), another GABA, receptor agonist (15), are also proconvulsant in 16day-old rats (16).…”

Section: Discussionmentioning

confidence: 99%

See 4 more Smart Citations

Age‐Related Differences in the Effects of GABA, Agonists Microinjected Into Rat Substantia Nigra: Pro‐ and Anticonvulsant Actions

Garant

Sperber

et al. 1995

Epilepsia

Self Cite

View full text Add to dashboard Cite

GABAergic transmission in the substantia nigra pars reticulata (SNR) has an important role in the control of experimental seizures. In the flurothyl seizure model, SNR microinjection of the selective GABAA receptor agonist muscimol results in a biphasic dose-response curve in adults: Intermediate doses are anticonvulsant, but high doses have proconvulsant effects. Another GABAA agonist, THIP (4,5,6,7-tetrahydroisoxazolo-[5,4-c]pyridin-3-ol), also produces anticonvulsant effects at lower doses, whereas higher doses tend to produce a proconvulsant effect. In 16-day-old rat pups, no anticonvulsant but only proconvulsant effects of muscimol occur, and at lower doses than in adults. These data suggest that the immature SNR is significantly more sensitive to the proconvulsant effects of GABAA receptor agonists than is the SNR of adults. We hypothesize that the age-related differences in nigral GABAergic response may be due to ontogenic changes in GABAA-sensitive neuronal circuits in the SNR.

show abstract

Section: Discussionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Age‐Related Differences in the Effects of GABA, Agonists Microinjected Into Rat Substantia Nigra: Pro‐ and Anticonvulsant Actions

Garant

Sperber

et al. 1995

Epilepsia

Self Cite

View full text Add to dashboard Cite

show abstract

Baclofen prevents rapid amygdala kindling in adult rats

Wurpel

1994

Experientia

View full text Add to dashboard Cite

This study investigates the effect of the gamma-aminobutyric acid (GABAB) agonist, baclofen, on amygdala kindling in adult rats. Baclofen has been reported to be anticonvulsant in a variety of seizure models and prevents kindling in immature rats. These experiments describe the effects of baclofen (2, 5 and 10 mg/kg, i.p.) on the afterdischarge threshold and kindling rate. Baclofen, 10 mg/kg, significantly increased the afterdischarge threshold in the amygdala. Baclofen at 5 and 10 mg/kg, retarded the rate of kindling as measured by the number of stimuli required to advance to subsequent seizure stages. These results suggest that baclofen may decrease the local excitability of the amygdala and retard the rate of seizure spread (or generalization) throughout the brain. Baclofen, acting at GABAB receptors exerts an anticonvulsant effect on amygdala kindling in these experiments.

show abstract

An indirect method for absorption rate estimation: Flurothyl-induced seizures

Lánský¹,

Velı́šková²,

Velı́šek³

1997

Bltn Mathcal Biology

View full text Add to dashboard Cite

This paper develops a method to estimate a minimal amount of flurothyl necessary to induce the seizures (the seizure threshold). A simple mathematical model is proposed which permits one to determine the drug absorption rate from the amount which has been administered and from the measured latency to onset of seizure. Experimental animal (rats) were exposed to a continuous intake of flurothyl in two different situations: either being alone in the airtight chamber or sharing it in a pair. In the latter case, we assume that the two rats uniformly share the infused drug. Our calculations estimate that approximately 20 microliters of flurothyl is necessary to induce twitches, whereas 25 microliters of flurothyl is the dose required for the induction of clonic seizures. The model can be used to estimate the threshold amounts of any drug producing obvious behavioral changes irrespective of the route of administration.

show abstract

The proconvulsant effect of nigral infusions of THIP on flurothyl-induced seizures in rat pups

Cited by 19 publications

References 19 publications

Age‐Related Differences in the Effects of GABA, Agonists Microinjected Into Rat Substantia Nigra: Pro‐ and Anticonvulsant Actions

Age‐Related Differences in the Effects of GABA, Agonists Microinjected Into Rat Substantia Nigra: Pro‐ and Anticonvulsant Actions

Baclofen prevents rapid amygdala kindling in adult rats

An indirect method for absorption rate estimation: Flurothyl-induced seizures

Contact Info

Product

Resources

About