Anticonvulsant-like actions of baclofen in the rat hippocampal slice.

1 The effects of baclofen were tested on epileptiform discharge in the rat hippocampal slice. Slices were superfused with bicuculline methiodide (100 microM) and maximal periods of afterdischarge were evoked by stimulating the Schaffer collateral-commissural pathway in area CA1, mossy fibres in area CA3 or perforant path fibres in the fascia dentata or by antidromic stimulation of CA1 pyramidal cells. 2 (-)-Baclofen attenuated the afterdischarge evoked by stimulating all three sets of fibres in areas CA1 and CA3. In each case, a threshold effect was observed at a concentration of 0.25 or 0.5 microM, and complete suppression was usually attained with a concentration of 5 microM. EC50 values ranged between 1 and 2 microM. (-)-Baclofen attenuated hippocampal afterdischarge with 120 times the potency of (+)-baclofen. It did not, however, affect the repetitive firing of dentate granule cells in response to stimulation of perforant path fibres. 3 (-)-Baclofen also reduced the amplitude of the initial population spike evoked by stimulation of Schaffer collateral-commissural fibres, but did not affect the antidromic population spike nor the initial population spike evoked by stimulation of the mossy fibres. 4 Recurrent inhibition in area CA1 was abolished by 1 microM (-)-baclofen. Thus baclofen, unlike many anticonvulsants, does not suppress afterdischarge by potentiating GABAergic inhibition. 5 These results suggest that baclofen attenuates hippocampal afterdischarge by a combination of pre- and postsynaptic mechanisms.

Duke Scholars

Author J. Victor Nadler Pharmacology & Cancer Biology