No abstract

The phenomenon of "one-trial tolerance" to the effects of chlordiazepoxide hydrochloride (CDP) in the elevated plus maze was re-examined. Unlike previous experiments, pre-exposure to the maze resulted in habituation and a consequential reduction in time spent on the open arms. The habituation effect was measured by recording the actual distance travelled by the rats in the maze and this was found to be significantly reduced by pre-exposure. Pre-exposure to the maze in the presence of CDP resulted in a reduced response to its "anxiolytic-like" effects (increasing time on the open arms compared to vehicle control rats). However, although the time spent on the open arms was reduced by pre-exposure, CDP significantly increased the time spent on the open arms by rats pre-exposed under a non-drugged state. These results suggest that rats do not become tolerant to the effects of CDP, but rather the reduced response to CDP after pre-exposure is due to habituation of exploratory behaviour.

The effects of the muscarinic antagonists scopolamine HBr and MeBr, the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), and the N-methyl-d-aspartate (NMDA) antagonists MK-801 and CGS-19755 on performance of rats in a delayed matching-to-position task were examined. Pretreatment with scopolamine HBr (0.05 and 0.1 mg/kg), resulted in a delay-dependent decrease in the percentage of correct responses and discriminability (log d), but had no effect on either the latency to complete trials, or the rate of trial completion during the fixed duration session. Scopolamine MeBr (0.1 mg/kg) did not impair percent correct or increase the response latency but did decrease the rate of trial completion. 8-OH-DPAT (up to 0.3 mg/kg), had no effect on percent correct, but did induce a small decrease in discriminability. The impairment in discriminability occurred only at a dose that substantially reduced the rate of trial completion. Both MK-801 (0.05 mg/kg) and CGS 19755 (10 mg/kg) induced a delay-independent impairment in percent correct, discriminability and a reduction in the rate of trial completion without affecting latency. A lower dose of CGS 19755 (5.0 mg/kg) induced a slight impairment in discriminability without significantly affecting the other measures. Taken together, these results demonstrate some dissociation between drug-induced cognitive and motor/motivational deficits in the DMTP test. However, the data question the specificity of putative cognitive impairments reported in many previous studies with the 5-HT1A agonist 8-OH-DPAT.

No abstract

Lamotrigine's anxiolytic effect in the CER test may be mediated via block of Na+ channels, and this may represent a target for the development of novel anxiolytics.