Khanna J M, Morato G S, Chau A, Shah G
Department of Pharmacology, University of Toronto, Canada.
Pharmacol Biochem Behav. 1995 Nov;52(3):609-14. doi: 10.1016/0091-3057(95)00149-q.
In a recent study, we showed that D-cycloserine, an agonist at the glycine site of the NMDA receptor, enhances the development of rapid tolerance to ethanol. In the present study, we report that the acquisition of rapid tolerance to the motor incoordination effect of ethanol (tilt-plane test) was increased only when D-cycloserine was injected before, but not after, the intoxicated practice under ethanol. The effect of D-cycloserine on tolerance when this agonist was administered in divided doses before and after test was similar to that obtained when D-cycloserine was injected before test. Higher doses of D-cycloserine did not produce a further enhancement of rapid tolerance. Moreover, when the dose of ethanol on day 1 was large enough to induce rapid tolerance per se, D-cycloserine did not further enhance the tolerance. The enhancement of tolerance by D-cycloserine was antagonized by previous administration of ketamine. The enhancement of ethanol tolerance by D-cycloserine and the antagonism of this effect by ketamine cannot be attributed to changes in pharmacokinetics of ethanol. Taken together, these results confirm the participation of the NMDA receptor system in the development of tolerance to ethanol, and reinforce earlier findings about the involvement of learning in tolerance.
在最近的一项研究中，我们发现D-环丝氨酸，一种N-甲基-D-天冬氨酸受体甘氨酸位点的激动剂，会加速对乙醇快速耐受性的形成。在本研究中，我们报告称，只有在乙醇中毒练习之前而非之后注射D-环丝氨酸时，对乙醇运动不协调效应（倾斜平面试验）的快速耐受性的获得才会增加。当在试验前后分剂量给予这种激动剂时，D-环丝氨酸对耐受性的影响与在试验前注射D-环丝氨酸时相似。更高剂量的D-环丝氨酸并不会进一步增强快速耐受性。此外，当第1天的乙醇剂量大到足以本身诱导快速耐受性时，D-环丝氨酸并不会进一步增强耐受性。先前给予氯胺酮可拮抗D-环丝氨酸对耐受性的增强作用。D-环丝氨酸对乙醇耐受性的增强以及氯胺酮对这种作用的拮抗作用不能归因于乙醇药代动力学的变化。综上所述，这些结果证实了N-甲基-D-天冬氨酸受体系统参与了对乙醇耐受性的形成，并强化了先前关于学习参与耐受性形成的研究结果。
