Comparison of the effects of full and partial allosteric modulators of GABA(A) receptors on complex behavioral processes in monkeys
- PMID:11224341
Comparison of the effects of full and partial allosteric modulators of GABA(A) receptors on complex behavioral processes in monkeys
Abstract
Two baselines involving a repeated acquisition task were used to assess the effects of bretazenil, imidazenil, and triazolam. The first baseline was a multiple schedule of repeated acquisition and performance of conditional discriminations. In the first component, the subject acquired a four-response chain by responding sequentially on three keys in the presence of different combinations of colors and geometric forms displayed on a center key. Acquisition of the discrimination was defined by a decrease in errors as the session progressed. In the performance component, the four-response chain was the same each session. Incorrect responses in either component produced a 5s time out during which responding had no programmed consequence. The second procedure, which has been used to evaluate the effects of drugs on memory, involved the acquisition of a discrimination, followed by a 1h delay and a retest of the same discrimination to assess retention. Triazolam (0.32 and 0.56mg/kg) administered alone, produced dose-related decreases in response rate in each component. In addition, triazolam also produced a dose-related increase in percentage errors in acquisition with no effect in performance. Triazolam (0.32mg/kg) eliminated retention (0 percent savings) in the memory task. Bretazenil (0.1-5.6mg/kg) or imidazenil (0.1-1.8mg/kg) administered alone had little or no effect on either rate of responding or accuracy in either component. Furthermore, bretazenil but not imidazenil disrupted retention at the higher doses tested. The combination of imidazenil or bretazenil with triazolam produced dose-related attenuation of the disruptive effects of triazolam on both behavioral baselines. These data suggest that the disruptive effects of benzodiazepines on learning and memory may be a function of the intrinsic efficacy of these compounds at different GABA(A) receptor subtypes.
Similar articles
- Imidazenil, a new anxiolytic and anticonvulsant drug, attenuates a benzodiazepine-induced cognition deficit in monkeys.Thompson DM, Auta J, Guidotti A, Costa E.Thompson DM, et al.J Pharmacol Exp Ther. 1995 Jun;273(3):1307-12.J Pharmacol Exp Ther. 1995.PMID:7791102
- Discriminative stimulus effects of benzodiazepine agonists and partial agonists in pentobarbital-trained rhesus monkeys.Rowlett JK, Woolverton WL.Rowlett JK, et al.Behav Pharmacol. 1998 Mar;9(2):81-92.Behav Pharmacol. 1998.PMID:10065928
- Effects of competitive and noncompetitive GABA(A) antagonists on the acquisition of a discrimination in squirrel monkeys.Pakarinen ED, Moerschbaecher JM.Pakarinen ED, et al.Behav Pharmacol. 1995 Mar;6(2):156-166.Behav Pharmacol. 1995.PMID:11224323
- Differential effects of prototype opioid agonists on the acquisition of conditional discriminations in monkeys.Moerschbaecher JM, Thompson DM.Moerschbaecher JM, et al.J Pharmacol Exp Ther. 1983 Sep;226(3):738-48.J Pharmacol Exp Ther. 1983.PMID:6887010
- An experimental analysis of the effects of d-amphetamine and cocaine on the acquisition and performance of response chains in monkeys.Thompson DM, Moerschbaecher JM.Thompson DM, et al.J Exp Anal Behav. 1979 Nov;32(3):433-44. doi: 10.1901/jeab.1979.32-433.J Exp Anal Behav. 1979.PMID:117072Free PMC article.
Cited by
- Relative potency and effectiveness of flunitrazepam, ethanol, and beta-CCE for disrupting the acquisition and retention of response sequences in rats.Leonard ST, Gerak LR, Delatte MS, Moerschbaecher JM, Winsauer PJ.Leonard ST, et al.Behav Pharmacol. 2009 Feb;20(1):33-44. doi: 10.1097/FBP.0b013e3283242f2d.Behav Pharmacol. 2009.PMID:19179849Free PMC article.
- Effects of GABA modulators on the repeated acquisition of response sequences in squirrel monkeys.Campbell UC, Winsauer PJ, Stevenson MW, Moerschbaecher JM.Campbell UC, et al.J Exp Anal Behav. 2004 Jul;82(1):37-56. doi: 10.1901/jeab.2004.82-37.J Exp Anal Behav. 2004.PMID:15484870Free PMC article.
- Alcohol effects on human risk taking.Lane SD, Cherek DR, Pietras CJ, Tcheremissine OV.Lane SD, et al.Psychopharmacology (Berl). 2004 Feb;172(1):68-77. doi: 10.1007/s00213-003-1628-2. Epub 2003 Nov 25.Psychopharmacology (Berl). 2004.PMID:14647967Clinical Trial.
- Effects of pregnanolone and flunitrazepam on the retention of response sequences in rats.Amato RJ, Moerschbaecher JM, Winsauer PJ.Amato RJ, et al.Pharmacol Biochem Behav. 2011 Sep;99(3):391-8. doi: 10.1016/j.pbb.2011.05.023. Epub 2011 May 27.Pharmacol Biochem Behav. 2011.PMID:21640749Free PMC article.
- Imidazenil prevention of alprazolam-induced acquisition deficit in patas monkeys is devoid of tolerance.Auta J, Guidotti A, Costa E.Auta J, et al.Proc Natl Acad Sci U S A. 2000 Feb 29;97(5):2314-9. doi: 10.1073/pnas.97.5.2314.Proc Natl Acad Sci U S A. 2000.PMID:10696114Free PMC article.
LinkOut - more resources
Full Text Sources
Other Literature Sources