A Couëtoux du Tertre

Saint Mary's Hospital Center, Montréal, Quebec, Canada

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Publications (8)41.08 Total impact

  • M Hascoet, M Bourin, A Couetoux du Tertre
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    ABSTRACT: A single prior undrugged exposure to the four-plate test reduces punished responding on retest at intervals ranging from 24 h to 42 days. Furthermore, prior experience attenuates the anxiolytic response to the benzodiazepines diazepam (0.25 to 2 mg/kg) and lorazepam (0.5 to 4 mg/kg). The result was first discussed in term of "one trial tolerance." The anxiety baseline was increased during the retest, which counteracted the anxiolytic action of benzodiazepines. To ascertain if memory processes are also implicated, the cholinergic drugs scopolamine and oxotremorine were used. Additional experiments with the GABAergic inverse agonist FG7142 and with the 5-HT1A receptor agonist 8-OH-DPAT were also performed. Administration of scopolamine and 8-OH-DPAT-induced weak impairment of memory, when administered before the second trial, but no effect was seen with cognition enhancing agents.
    Pharmacology Biochemistry and Behavior 01/1998; 58(4):1131-8. · 2.82 Impact Factor
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    ABSTRACT: We investigated whether the selective brain cholecystokinin (CCKB) receptor antagonist, L-365,260, could antagonize the panicogenic effects of CCK-tetrapeptide (CCK-4) in patients with panic disorder. The study employed a double-blind, placebo-controlled, two-period crossover design. Patients (N = 29) received a single oral dose of L-365,260 (10 or 50 mg) or placebo 90 minutes prior to injection of CCK-4. After a 1-week washout period, patients received a different dose of L-365,260 or placebo according to a balanced incomplete block design. The 50-mg dose of L-365,260 was superior to placebo in reducing the number (P < .01) and sum intensity (P < .001) of symptoms induced with CCK-4. Panic attack frequency following CCK-4 injection was 88% for patients receiving placebo, 33% for those receiving the 10-mg dose, and 0% for those receiving the 50-mg dose. The difference between the effects of the 50-mg dose and placebo was statistically significant (P = .002). Increases in heart rate following CCK-4 injection were markedly reduced with both the 50-mg (P < .0001) and 10-mg (P < .01) doses compared with placebo. These data suggest that CCKB receptors are an important site of action of exogenous CCK-4. It will be important to determine in future studies the efficacy of CCKB receptor antagonists as antipanic agents.
    Archives of General Psychiatry 06/1994; 51(6):486-93. · 13.77 Impact Factor
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    ABSTRACT: The neuropeptide cholecystokinin-tetrapeptide (CCK-4) has potent anxiogenic action in human and animal subjects. On the basis of prior work which demonstrated that benzodiazepine (BZD) receptor agonists antagonized CCK-induced excitation of rat hippocampal neurons we studied whether BZD receptors mediated the anxiogenic effect of CCK-4. To examine this possibility we determined whether the BZD receptor antagonist flumazenil could antagonize the effects of CCK-4 (50 g) in healthy volunteers. Thirty subjects (10 females; 20 males) were pretreated with flumazenil (2 mg in saline) or placebo (0.9% NaCl in water) 15 min prior to CCK-4 challenge in a randomized double-blind crossover design. Flumazenil had no impact on the behavioral and cardiovascular effects of CCK-4, suggesting that BZD receptors do not mediate the anxiogenic action of CCK-4. The influence of GABA and non-GABA-related mechanisms on response to CCK-4 remains to be considered.
    Psychopharmacology 02/1994; 114(2):257-261. · 4.06 Impact Factor
  • M Bourin, A Couëtoux du Tertre, M C Colombel, J L Auget
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    ABSTRACT: The effects of low oral doses of lorazepam on several cognitive and performance tasks were investigated in 50 healthy students. A double-blind, parallel group design was used to compare five treatments: placebo and lorazepam 0.5, 0.75, 1 mg and progressive doses up to 1.5 mg. After randomization, all subjects received placebo for 3 days in a single-blind procedure followed by five consecutive days of treatment. Subjects completed a battery of tests each day of the 5 days active treatment and the day after stopping the treatment. There were no significant differences between placebo and lorazepam on the free recall test and the critical flicker fusion frequency test, but lorazepam produced significant improvement on the digit symbol substitution test and the choice reaction time test. We suggest that low repeated doses of lorazepam in healthy subjects improve the psychomotor performance without sedation and memory impairment.
    International Clinical Psychopharmacology 02/1994; 9(2):83-8. · 2.71 Impact Factor
  • M. Bourin, A. Couetoux du Tertre, R. Payeur
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    ABSTRACT: Argues that it is necessary to look for changes induced by anxiolytics on vital signs, laboratory parameters, and adverse affects. The authors examine side effects at the CNS level with psychological and physiological battery tests. The most commonly used psychological assessments test image recognition, digit symbol substitution, choice reaction time (RT), critical flicker fusion, and cognitive functions. They also assess the safety of use of anxiolytics in certain specific conditions, such as overdose or withdrawal and in certain populations such as the elderly, neonates, and children. Elderly patients respond differently (than younger patients) to benzodiazepines (BZs). Alcohol can potentiate the action of BZs. The assessment of safety and side effects, whatever the drug type studied, must come early in the developing process of a drug. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
    European Psychiatry 01/1993; · 3.29 Impact Factor
  • J Bradwejn, D Koszycki, L Annable, A Couëtoux du Tertre, S Reines, C Karkanias
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    ABSTRACT: Recent animal studies have shown that pretreatment with centrally active cholecystokinin (CCK) antagonists blocks the anxiogenic effects of CCK-tetrapeptide (CCK-4). In order to determine whether pretreatment with these antagonists can block the anxiogenic effects of CCK-4 in patients with panic disorder, a suitable challenge dose of CCK-4 must be selected. Thus, we conducted a dose range study in which patients with panic disorder (n = 29) were challenged with CCK-4 (10, 15, 20, or 25 micrograms) or placebo on two separate occasions, in a balanced incomplete block design. Patients received in random order 10 micrograms (n = 12), 15 micrograms (n = 11), 20 micrograms (n = 12), or 25 micrograms (n = 12) of CCK-4 or placebo (n = 11). CCK-4 induced anxiety and panic responses in a dose-dependent fashion. The incidence of panic attacks following the CCK-4 challenge was 17% (10 micrograms), 64% (15 micrograms), 75% (20 micrograms), and 75% (25 micrograms). None of the patients panicked with placebo. Moreover, a strong linear relationship between CCK-4 and increases in heart rate and diastolic blood pressure was found. The findings of this study suggest that a dose of 20 micrograms of CCK-4 (ED75) might be suitable for efficacy studies of CCKB antagonists and other potential antipanic drugs in patients with panic disorder.
    Biological Psychiatry 12/1992; 32(10):903-12. · 9.25 Impact Factor
  • M Bourin, A Couetoux du Tertre
    Clinical Neuropharmacology 02/1992; 15 Suppl 1 Pt A:224A-225A. · 1.82 Impact Factor
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    ABSTRACT: It has been suggested that cholecystokinin, a neurotransmitter found in high density in mammalian brain, might be implicated in the neurobiology of panic and anxiety disorders. Cholecystokinin-tetrapeptide induces panic attacks analogous to spontaneous panic attacks in patients suffering from panic disorder and to a much lesser degree in healthy volunteers, suggesting an enhanced sensitivity to cholecystokinin-tetrapeptide in panic disorder. In animal models of anxiety, pre-treatment with cholecystokinin antagonists significantly decreases the anxiogenic effects of cholecystokinin agonists. This paper reviews clinical and basic studies supporting an involvement for cholecystokinin in panic and anxiety disorders.
    Journal of Psychopharmacology 01/1992; 6(3):345-51. · 3.37 Impact Factor