Selective changes in the in vivo effects of benzodiazepine receptor ligands after chemical kindling with FG 7142

Pharmacology of the β‐Carboline FG‐7142, a Partial Inverse Agonist at the Benzodiazepine Allosteric Site of the GABAA Receptor: Neurochemical, Neurophysiological, and Behavioral Effects

“…The kindling effects of chronic FG‐7142 administration can be blocked with coadministration of a benzodiazepine antagonist, the imidazobenzodiazepine Ro 15–1788, administered either during kindling exposures or at the time of challenge following kindling (Little et al 1984). Chronic FG‐7142 treatment not only sensitizes the convulsant effects of subsequent administration of FG‐7142 or other β‐carboline inverse agonists such as β‐CCM and DMCM, but also decreases the anticonvulsant effects of β‐carboline (but not benzodiazepine) agonistic modulation of the GABA A receptor (Little et al 1986; Petersen and Jensen 1987; Little et al 1987a; Little et al 1987b). Chronic benzodiazepine (7 days flurazepam, 40 mg/kg i.p.)…”

Convulsions Induced by Methyl β‐Carboline‐3‐Carboxylate in Mice: Effects of Preceding Saline Injections

“…Thus, in these four strains, an effect (either tolerance or sensitization) or preliminary injection was noted, but that no difference was ever observed between saline-treated and P-CCM-treated mice ruled out both tolerance to the drug and kindling effects, at least under our experimental conditions. Although animal kindling has been observed with several GABA receptor ligands, such as PTZ (Craig and Colasanti, 1989;Corda et al, 1990a,b;Giorgi et al, 1991 ;Becker et al, 1992) or P-carbolines (Little et al, 1984(Little et al, , 1987Corda et al, 1988;Lewin et al, 1989), almost nothing is known about kindling in inbred mouse strains. Differences in olfactory bulb (classic) kindling were reported by Green and Seyfried (1991) between several inbred strains, including some used in our study (DBA/2, C57BL/6, C3H/ He).…”

“…It has been linked with GABA-mediated inhibition (Albertson et al, 1990;Sat0 et al, 1990), although other brain systems also appear to be involved, such as N-methyl-D-aspartate (NMDA) receptors (Burnham et al, 1989;Morimoto, 1989) or the adrenergic mechanism (Stanton et al, 1989;Applegate and Burchfiel, 1990). Chemical kindling is produced by repeated administration of subconvulsant doses of GABA receptor antagonists such as pentylenetetrazol (PTZ) (Craig and Colasanti, 1989;Corda et al, 1990a,b;Giorgi et al, 1991;Becker et al, 1992) or p-carbolines (Little et al, 1984(Little et al, , 1987Corda et al, 1988;Lewin et al, 1989). On the contrary, tolerance has been observed after repeated administration of BZD receptor agonists (File, 1981;Sannerud et al, 1989) and also after PTZ administration (Sierra-Paredes et al, 1989).…”

Serotonin 1A receptor autoradiography during alcohol-withdrawal kindling

“…Kindling is a process in which repeated applications of initially subconvulsive electrical stimulations eventually produce motor seizures and EEG alterations of progressing severity (Goddard et al 1969). Similarly, it has been demonstrated that seizure activity can be kindled pharmacologically by repeated administrations of di¤erent drugs such as cocaine, lidocaine, glutamate and the inverse benzodiazepine agonist FG 7142 (Little et al 1987;Post et al 1988;Stephens and Weidmann 1989;Weiss et al 1989;Croucher and Bradford 1990).…”