T P Durkin

Université Bordeaux 1, Talence, Aquitaine, France

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Publications (8)26.53 Total impact

  • T Maviel, T P Durkin
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    ABSTRACT: A delayed-matching spatial working memory protocol in a 5-arm maze was used to test the hypothesis of differential roles for central nicotinic and muscarinic cholinergic receptors in mediating task performance. In experiment 1, using a within subjects-repeated design, groups of C57Bl/6 mice, previously trained to criterion with a 4 h retention interval separating presentation and test phases, received i.p. injections of either saline, scopolamine (0.8 mg/kg), mecamylamine (8.0 mg/kg), or the combination of scopolamine and mecamylamine before re-testing. Injections were given either, a) 15 min pre-presentation or, b) 30 s, c) 15 min, d) 3 h 45 min post-presentation in order to differentially affect the acquisition, trace maintenance and recall phases. Significant decreases in correct responses were observed for each drug treatment but the effects were a function of the time of treatment. Results of condition d), (i.e.15 min before retention test) confirm previous reports of severe disruption by each antagonist and their combination on retention. However, conditions a-c) show a constant disruption by scopolamine, increasing disruption by mecamylamine, whereas the combined treatment was without effect. Although the data show that central nicotinic and muscarinic antagonists both modulate working memory performance, they indicate first, that scopolamine-induced "amnesia" results, not from selective post-synaptic M1 muscarinic blockade but from indirect over-activation of nicotinic receptors. Second, the observation of high levels of retention although nicotinic and muscarinic receptors had undergone combined blockade during a large part of the retention interval is incompatible with the concept that test-induced activation of central cholinergic neurones mediates memory trace maintenance. Finally, taken with data from experiment 2, using a short (20 min) treatment-to-test interval, we conclude that central nicotinic receptors play a key role in attentional processes enabling working memory trace access during retrieval.
    Neuroscience 02/2003; 120(4):1049-59. · 3.12 Impact Factor
  • Vincent David, Thomas P Durkin, Pierre Cazala
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    ABSTRACT: The involvement of dopamine neurotransmission in opiate reward remains controversial. To investigate the dopaminergic basis of opiate reward by comparing the effect of systemic injection of the D2/D3 antagonist sulpiride on morphine self-administration (ICSA) into the ventral tegmental area (VTA) or the nucleus accumbens (NAc) BALB/c mice were unilaterally implanted with a guide cannula 1.5 mm above either the VTA or the NAc. On experimental days, a stainless-steel injection cannula was inserted via the guide cannula, and mice were trained to discriminate the arm of a Y-maze reinforced by intracranial morphine microinjections (6.5 pmol or 65 pmol/50 nl) from the neutral arm (no injection). Following acquisition of morphine ICSA, the dopamine D2/D3 receptor antagonist sulpiride (50 mg/kg, i.p.) was administered 30 min before testing. Sulpiride produced an extinction of intra-VTA, but not intra-NAC, morphine self-administration. Extinction in VTA subjects was followed by a re-appearance of ICSA, although mice continued to receive sulpiride injections. Extinction was re-induced when the dose of sulpiride was raised to 100 mg/kg, whereas no effect of this dose was detected on intra-NAc self-administration. Maintenance of intra-VTA, but not intra-NAc, morphine self-administration depends acutely on D2/D3 receptors. However, the deleterious effect of sulpiride on intra-VTA morphine self-administration is transient. Reappearance of ICSA under neuroleptic treatment in VTA subjects may be related to the sensitization effect of intra-VTA morphine infusions, combined with an upregulation of D2/D3 receptors and alterations of DA metabolism by repeated sulpiride injections.
    Psychopharmacology 04/2002; 160(3):307-17. · 4.06 Impact Factor
  • Vincent David, Thomas P. Durkin, Pierre Cazala
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    ABSTRACT: Rationale: The involvement of dopamine neurotransmission in opiate reward remains controversial. Objective: To investigate the dopaminergic basis of opiate reward by comparing the effect of systemic injection of the D2/D3 antagonist sulpiride on morphine self-administration (ICSA) into the ventral tegmental area (VTA) or the nucleus accumbens (NAc) Methods: BALB/c mice were unilaterally implanted with a guide cannula 1.5mm above either the VTA or the NAc. On experimental days, a stainless-steel injection cannula was inserted via the guide cannula, and mice were trained to discriminate the arm of a Y-maze reinforced by intracranial morphine microinjections (6.5pmol or 65pmol/50nl) from the neutral arm (no injection). Following acquisition of morphine ICSA, the dopamine D2/D3 receptor antagonist sulpiride (50mg/kg, i.p.) was administered 30min before testing. Results: Sulpiride produced an extinction of intra-VTA, but not intra-NAC, morphine self-administration. Extinction in VTA subjects was followed by a re-appearance of ICSA, although mice continued to receive sulpiride injections. Extinction was re-induced when the dose of sulpiride was raised to 100mg/kg, whereas no effect of this dose was detected on intra-NAc self-administration. Conclusion: Maintenance of intra-VTA, but not intra-NAc, morphine self-administration depends acutely on D2/D3 receptors. However, the deleterious effect of sulpiride on intra-VTA morphine self-administration is transient. Reappearance of ICSA under neuroleptic treatment in VTA subjects may be related to the sensitization effect of intra-VTA morphine infusions, combined with an upregulation of D2/D3 receptors and alterations of DA metabolism by repeated sulpiride injections.
    Psychopharmacology 02/2002; 160(3):307-317. · 4.06 Impact Factor
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    ABSTRACT: A 5-arm maze was used to measure sustained visuo-spatial attention in C57Bl/6 mice and test the hypothesis of differential functional roles for central nicotinic and muscarinic receptors in mediating task performance. Mice were first trained to acquire the basic visual discrimination task in which, on each trial, one randomly chosen arm among the five open arms was baited and remained lit until an arm-choice was made. Mice were then submitted to attentional testing in which trials using light signals of 2, 1 or 0.5 s were intermixed to evaluate the decrement in correct responses as a function of the decrease in light signal duration and thus, to construct a reference curve for the attentional performance of C57Bl/6 mice. Mice were then divided into four groups and received, in rotation, over four pharmacological sessions according to a Latin-square design, i.p. injections of either mecamylamine (4.0 mg/kg), scopolamine (0.8 mg/kg), the combination of mecamylamine and scopolamine or saline, 20 min before re-testing. Injection of cholinergic antagonists produced decreases in percentage of correct responses, which were systematically associated with significant increases in choice latencies. Mecamylamine produced slight disruption, whereas scopolamine and the combined treatment both produced severe disruption. In conclusion, whereas both nicotinic and muscarinic cholinergic antagonists disrupt performance in the attentional task, the increase in response latencies entails that correct responding becomes more dependent on the working memory processes and thus compromises conclusions as to a selective disruption of attention.
    Behavioural Brain Research 02/2002; 128(1):91-102. · 3.33 Impact Factor
  • T P Durkin, C Beaufort, L Leblond, T Maviel
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    ABSTRACT: A 5-arm maze has been developed to provide parallel tests of sustained visuo-spatial attention and spatial working memory in mice. C57Bl/6 mice were trained to select, either by immediate response (attention) or by delayed-matching response (working memory), one target arm among the five open arms. For attention testing, mice were first trained to acquire the basic task in which one randomly selected baited arm remained lit until a choice was made. Criterion of >80% correct with a response latency <5 s was attained in 52-56 trials. Following this, attention was tested by using trials wherein light signal durations of 2, 1 or 0.5 s were intermixed to vary attentional load. In the working memory test, mice were submitted to a forced visit to a randomly selected baited arm during a presentation phase. Following a variable retention interval (R.I.), mice were replaced into the maze and rewarded for choosing this arm. Criterion of >80% correct was attained in 35-40 trials and mice exhibited high levels of retention for R.I.s up to 4 h. Results validate the 5-arm maze for evaluation of both sustained visuo-spatial attention and spatial working memory in mice. Both the tasks are rapidly acquired and the 20% chance level provides high resolution for evaluating performance. This comparative strategy allows to dissociate attention and memory and to reveal deficits in these processes during ageing or in knockout strains. The high level of retention performance over R.I.s of 4 h enables studies using pharmacological treatments differentially affecting the acquisition, encoding, retention or retrieval phases of working memory. Furthermore, functional brain imaging studies may be used to identify neuronal networks which are differentially activated during these distinct phases.
    Behavioural Brain Research 12/2000; 116(1):39-53. · 3.33 Impact Factor
  • V David, T P Durkin, P Cazala
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    ABSTRACT: In order to study the functional role of the trans-synaptic neuronal interaction between glutamatergic afferents and mesolimbic dopaminergic neurons in internal reward processes, BALB/c male mice were unilaterally implanted with a guide-cannula, the tip of which was positioned 1.5 mm above the ventral tegmental area (VTA). On each day of the following experimental period, a stainless steel injection cannula was inserted into the VTA in order to study the eventual self-administration behaviour of either the competitive N-methyl-D-aspartate antagonist, D(-)-2-amino-7-phosphonoheptanoic acid (AP-7) or the alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid antagonist, 6,7-dinitroquinoxaline-2,3-dione (DNQX) (3 ng/50 nL) using a spatial discrimination task in a Y maze. Mice rapidly discriminated between the arm enabling a microinjection of either of these glutamatergic antagonists and the neutral arm of the maze, and a robust self-administration of either of these compounds was observed from the first session of acquisition. These data provide strong evidence that the intra-VTA microinjection of either of these subclasses of glutamatergic antagonist produces an effect which is interpreted centrally by the experimental subjects as being highly rewarding. Once the self-administration response had been fully acquired by the experimental subjects, preinjection of the dopaminergic D2 antagonist, sulpiride (50 mg/kg i.p.), 30 min before the test, produced a rapid extinction of the self-administration response. This latter result demonstrates the dopaminergic D2 receptor dependence of this intra-VTA self-administration of both of these subclasses of glutamatergic antagonist. We conclude that the different glutamatergic afferent neuronal inputs to the VTA globally exert, in vivo, via the mediation of interposed endogenous GABAergic interneurons, a tonic trans-synaptic inhibitory regulation of neuronal activity in the mesolimbic dopaminergic pathway and that this complex neuronal interaction in the VTA plays a significant functional part in the modulation of internal reward processes.
    European Journal of Neuroscience 05/1998; 10(4):1394-402. · 3.75 Impact Factor
  • T. P. Durkin, C. Beaufort, T. Maviel, L. Leblond
    Journal of Physiology-Paris 01/1998; 92(5):427-428. · 0.82 Impact Factor
  • V David, T P Durkin, P Cazala
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    ABSTRACT: BALB/c mice were unilaterally implanted with a guide cannula, the tip of which was positioned 1.5 mm above the ventral tegmental area (VTA). On each day of the experimental period, a stainless steel injection cannula was inserted into the VTA in order to study the eventual self-administration of a low dose (1.5 ng/50 nl) of bicuculline, a GABAA-antagonist, using a spatial discrimination task in a Y maze. Mice rapidly discriminated between the arm enabling a micro-injection of bicuculline and the neutral arm of the maze, and robust self-administration of this GABAergic antagonist was observed. Once this self-administration response for bicuculline had been fully acquired, the systemic injection of the dopaminergic D2 antagonist sulpiride (50 mg/kg), 30 min before the test, produced a rapid extinction of the self-administration response. Moreover, if this same sulpiride pretreatment was given during the initial acquisition period mice did not discriminate between the two arms of the Y-maze. These data demonstrate the dopamine D2 dependence of this bicuculline self-administration behavior, and confirm that GABAergic interneurons and/or inputs normally transynaptically inhibit neuronal activity in the mesocorticolimbic dopamine system.
    Psychopharmacology 04/1997; 130(2):85-90. · 4.06 Impact Factor