T P Durkin

University of Bordeaux, Burdeos, Aquitaine, France

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Publications (4)15.94 Total impact

  • 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
  • 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
  • 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