Chlordiazepoxide interactions with scopolamine and dizocilpine: Novel cooperative and antagonistic effects on spatial learning.

Abstract

The authors investigated the effects on spatial behavior of coadministrations of a benzodiazepine, chlordiazepoxide (CDP), with a noncompetitive N-methyl-d-aspartate receptor antagonist (NMDAR), dizocilpine (DZP), and a muscarinic cholinergic receptor antagonist, scopolamine (SCP). Rats solved the Morris swim task in 2 settings; 1 in which a hidden escape platform was always in the same location (performance) and a 2nd in which the platform had been moved to a different location (acquisition) for repeated daily sessions. CDP (3.0 mg/kg) administered alone did not disrupt escape latencies or swim path accuracies. SCP and DZP each impaired acquisition and performance in a dose-dependent manner. CDP coadministered with 0.3 mg/kg SCP impaired escape only in the acquisition setting and when coadministered with 1.0 mg/kg SCP selectively exacerbated the escape impairment in the acquisition setting. CDP ameliorated deleterious effects of DZP in both settings.

Chlordiazepoxide and dizocilpine, but not morphine, selectively impair acquisition under a novel repeated-acquisition and performance task in rats

“…The present data with CDP are consistent with those obtained in the RAP/MST with rats (Keith and Galizio 1997;Keith et al 2003;Padlubnaya et al 2005) and with those from other RAP tasks in a variety of species (e.g., Bickel et al 1991;Auta et al 1995;Winsauer et al 1996;Campbell et al 2004). It should be noted, however, that positive GABA A modulation does not guarantee that acquisition-selective effects will be observed.…”

“…In another stimulus context, rats swim to a submerged platform that remains in the same position from session to session (the performance component). The benzodiazepines chlordiazepoxide (CDP) and midazolam (MDZ) consistently impair spatial acquisition in this RAP/MST at doses that do not affect performance (Keith and Galizio 1997;Keith et al 2003;Padlubnaya et al 2005). These selective effects on spatial acquisition are similar to those typically reported with benzodiazepines under RAP procedures with response sequences (e.g., Auta et al 1995;Winsauer et al 1996;Campbell et al 2004).…”

Fluoxetine and the dentate gyrus: memory, recovery of function, and electrophysiology

“…Although the adaptation of the MWT that was used in this study has also been used in earlier studies that examined the pharmacology of spatial learning, the effects of DG damage under this particular procedure had not been reported previously Keith et al, 2003;Padlubnaya et al, 2005). Colchicine microinjections into the DG profoundly impaired the reference-memory and matchingto-place performances during the early postoperative period, confirming that the DG is essential for the adaptation of the MWT procedure used here.…”

“…Therefore, there was little scope for the observation of further improvement that could have been produced by fluoxetine. In contrast, the procedure used here was very well suited for detecting drug-induced disturbances, either in reference memory or in matching-to-place memory; earlier work by our laboratory has demonstrated that very subtle changes from steady-state baseline are more readily detected using the present procedure than by between-group procedures Keith et al, 2003;Padlubnaya et al, 2005). Numerous studies based on clinical populations have reported that fluoxetine can cause memory disturbances in depressed patients (Mirow, 1991;Bradley and Kulik, 1993;Bangs et al, 1994;Friedman, 1994;Joss et al, 2003;Huang et al, 2004).…”

Validation and scopolamine-reversal of latent learning in the water maze utilizing a revised direct platform placement procedure

“…The sensory and attentional demands of swimming to visible and invisible platforms may be somewhat different. Therefore, it would be of further interest to compare scopolamine effects on swimming back to an invisible platform under two conditions: repeatedly swimming back to a constant location, versus a continually changing platform location, where a new spatial memory must be acquired each day (Keith and Galizio, 1997;Padlubnaya et al, 2005).…”