Role of Frontal Cortex in the Development of Methamphetamine-induced Reverse Tolerance

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Low dose of sulpiride, which is a selective D_2-receptor blocker, is thought to block DA autoreceptor preferencially. But our previous experiments did not provide the findings supporting this hypothesis. Results of our experiments showed that low dose of sulpiride preferencially blocked DA neurotransmission in frontal cortex. Present result, which shows that low dose of sulpiride reverses methamphetamine-induced contralateral rotation of unilateral frontal cortex ablation rats, indicates its preferencial blockade of frontal DA neurotransmission. But, in the experiment used with in vivo brain dialysis method, low dose sulpiride increases extracellular DA content in same extent but more slowly compared with high dose sulpiride. Accordingly the possibility that low dose sulpiride blocks preferencially DA autoreceptor is undeniable from this result. Our present results indicates that low dose sulpiride preferencially blocks frontal cortex DA transmission and/or DA autoreceptor.Neurochemical basis of methamphetamine-induced reverse tolerance is thought to be manifestation of subsensitivity of DA autoreceptor and hypofunction of frontal DA neurotransmission. these subsensitivity and hypofunction are result of repeate DA stimulation by methamphetamine treatment. Therefor, the blockade of Frontal DA neurotransmission and DA autoreceptor might inhibit the development of reverse tolerance. In present main experiment, low dose sulpiride treatment ptrecedes each methamphetamine treatment. But rats with this combination drug treatment exhibit reverse tolerance in same degre with rats injected with repeated methamphetamine alone. This result indicates that another biochemical mechanism implicated in the development of reverse tolerance.