Effects of convulsant and anticonvulsant agents on memory in squirrel monkeys

Pakarinen, Eric D.; Faust, W. B.; Moerschbaecher, Joseph M.

doi:10.1016/0278-5846(96)00066-8

Cited by 10 publications

(9 citation statements)

References 24 publications

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“…These results are consistent with previous findings indicating that cocaine and other CNS stimulants can produce acute disruptions of learning in animals as well as humans responding under comparable repeated-acquisition procedures (Thompson 1977;Fischman 1978;Thompson and Moerschbaecher 1979;Moerschbaecher and Thompson 1980). Such procedures have also been used to show that positive GABA A modulators could produce disruptions of learning in animals as well as humans (Thompson 1973;Desjardins et al 1982;Pakarinen et al 1996;Winsauer et al 1996;Gerak et al 2004). Similar to most studies performed with humans and monkeys, the effects of lorazepam and pregnanolone in the current study were more selective for responding in the acquisition component; that is, errors were increased in the acquisition component at doses of pregnanolone or lorazepam smaller than those that increased errors in the performance component.…”

Section: Discussionsupporting

confidence: 90%

Interaction of cocaine with positive GABAA modulators on the repeated acquisition and performance of response sequences in rats

et al. 2005

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Section: Discussionsupporting

confidence: 90%

Interaction of cocaine with positive GABAA modulators on the repeated acquisition and performance of response sequences in rats

et al. 2005

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“…Thus, ␦-opioid receptor agonists may have therapeutic potential as analgesic agents, especially in hyperalgesia and allodynia (e.g., Negus et al, 1994;Fraser et al, 2000). Unfortunately, BW373U86 displays dose-dependent convulsive activity upon systemic administration to mice (Comer et al, 1993a), rats (Broom et al, 2002), and monkeys (Dykstra et al, 1993;Negus et al, 1994;Pakarinen et al, 1996).…”

mentioning

confidence: 99%

Comparison of Receptor Mechanisms and Efficacy Requirements for δ-Agonist-Induced Convulsive Activity and Antinociception in Mice

Broom

Nitsche²,

Pintar³

et al. 2002

J Pharmacol Exp Ther

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␦-Opioid receptor-selective agonists produce antinociception and convulsions in several species, including mice. This article examines two hypotheses in mice: 1) that antinociception and convulsive activity are mediated through the same type of ␦-receptor and 2) that greater ␦-agonist efficacy is required for antinociception than for convulsive activity. ␦-Mediated antinociception was evaluated in the acetic acid-induced abdominal constriction assay, which involves a low-intensity noxious stimulus; convulsive activity was indicated as a mild tonic-clonic convulsive episode followed by a period of catalepsy. In ␦-opioid receptor knockout mice [DOR-1(Ϫ/Ϫ)], the nonpeptidicfailed to produce convulsive behavior demonstrating the absolute involvement of DOR-1 in this effect. In NIH Swiss mice expressing ␦-opioid receptors, BW373U86 produced both antinociception and convulsive activity. These effects were antagonized by the putative ␦ 1 -receptor-selective antagonist 7-benzylidenenaltrexone and the putative ␦ 2 -receptor-selective antagonist naltriben. Tolerance developed to both the convulsive and antinociceptive effects of BW373U86. Tolerance to the convulsive, but not the antinociceptive, effects of BW373U86 was largely prevented when the antagonist naltrindole was given 20 min after each dose of the agonist in a 3-day treatment paradigm. The convulsive action of BW373U86 was also less sensitive than the antinociceptive action to treatment with the irreversible ␦-antagonist naltrindole isothiocyanate. Collectively, these data suggest that the convulsive and antinociceptive activities of ␦-agonists are mediated through the same receptor but that the receptor reserve for ␦-mediated convulsive activity is greater than for ␦-mediated antinociceptive activity.

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“…Using a similar baseline to the one used in the present study, these investigators administered convulsants such as strychnine and pentylenetetrazole that directly inhibit the GABA A receptor complex and found that they had no effect on retention compared to triazolam when they were administered immediately after acquisition of the sequence or 24 h prior to retention. Therefore, one of the conclusions of the study by Pakarinen et al (1996) was that these convulsants drugs, which inhibit the chloride influx through the GABA A receptor complex, neither enhanced nor disrupted memory in squirrel monkeys responding under this memory task involving repeated acquisition at subconvulsant doses.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, in this study by Auta et al (1995), both imidazenil and bretazenil were able to antagonize the memory-disrupting effects of triazolam, a full positive allosteric modulator, at doses that had no effect on response rate, percent savings or percent error. A study by Pakarinen et al (1996) involving squirrel monkeys also indicated how efficacy as a positive modulator is required to disrupt memory processes. Using a similar baseline to the one used in the present study, these investigators administered convulsants such as strychnine and pentylenetetrazole that directly inhibit the GABA A receptor complex and found that they had no effect on retention compared to triazolam when they were administered immediately after acquisition of the sequence or 24 h prior to retention.…”

Section: Discussionmentioning

confidence: 99%

Relative potency and effectiveness of flunitrazepam, ethanol, and beta-CCE for disrupting the acquisition and retention of response sequences in rats

Leonard

Gerak

Delatte

et al. 2009

Behavioural Pharmacology

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Despite the knowledge that GABA A modulators can affect learning and memory, their capacity for disrupting each of these complex processes is rarely compared, and often mistakenly assumed to occur with identical potency. For these reasons, the effects of flunitrazepam (0.056-3.2 mg/kg), ethanol (0.25-1.5 g/kg), and β-CCE (ethyl-β-carboline-3-carboxylate; 1-17.8 mg/kg) were compared in groups of rats responding under baselines that assessed learning and memory separately. The first baseline was a multiple schedule of repeated acquisition and performance of tandem response sequences, whereas the second baseline was a retention or memory procedure where a tandem response sequence was acquired and then retested after a 30-min delay. Under both procedures, responding was maintained under a second-order fixed-ratio (FR) 2 schedule of food reinforcement, and incorrect responding (errors) produced a 5-sec timeout. With regard to the effects of the three drugs on sequence acquisition (learning), all three drugs dose-dependently decreased the overall response rate and increased the percentage of errors. Both flunitrazepam and β-CCE affected accuracy more potently than response rate, whereas ethanol was equipotent in affecting these two dependent measures. With regard to the effects of these drugs on sequence retention (memory), both flunitrazepam and ethanol dose-dependently decreased retention at doses that had little or no effect on sequence acquisition under the multiple schedule, whereas β-CCE decreased retention and sequence acquisition similarly at the doses tested. Together, these data demonstrate that drugs with differing capacities for altering the function of GABA A receptors differ in their capacity for disrupting the acquisition and retention of response sequences and that positive modulation of this receptor complex may be more predictive of disruptions in memory than disruptions in learning.

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Effects of convulsant and anticonvulsant agents on memory in squirrel monkeys

Cited by 10 publications

References 24 publications

Interaction of cocaine with positive GABAA modulators on the repeated acquisition and performance of response sequences in rats

Interaction of cocaine with positive GABAA modulators on the repeated acquisition and performance of response sequences in rats

Comparison of Receptor Mechanisms and Efficacy Requirements for δ-Agonist-Induced Convulsive Activity and Antinociception in Mice

Relative potency and effectiveness of flunitrazepam, ethanol, and beta-CCE for disrupting the acquisition and retention of response sequences in rats

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