Neuronal adaptations involving dopaminergic, glutamatergic, and serotonergic neurotransmitter systems are responsible for behavioral sensitization. Because of common underlying mechanisms, cross-sensitization between compounds of different drug classes can be observed. The purpose of the present study was to determine whether a one- or four-day pretreatment regimen of RU 24969 (a 5-HT_1A/1B receptor agonist) would reciprocally cross-sensitize with cocaine or methamphetamine in male and female preweanling rats. Rats were pretreated with RU 24969 (0 or 5 mg/kg) for 4 days (PD 17–20) and then challenged with cocaine (10 or 20 mg/kg) or methamphetamine (1 or 2 mg/kg) on PD 22. Reciprocal cross-sensitization was also assessed (i.e., rats were pretreated with psychostimulants and tested with RU 24969). In a follow-up experiment, the ability of RU 24969 and cocaine to reciprocally cross-sensitize was assessed using a one-day pretreatment regimen. Reciprocal cross-sensitization between cocaine and RU 24969 was evident in preweanling rats, whereas methamphetamine and RU 24969 did not cross-sensitize. When a one-trial pretreatment regimen was used, cross-sensitization was only detected when rats were pretreated with RU 24969 and tested with cocaine, but not the reverse. In sum, the present results show that the nonselective 5-HT_1A/1B receptor agonist RU 24969 cross-sensitizes with cocaine, but not methamphetamine, in preweanling rats. This dichotomy may be a function of cocaine having a greater affinity for the serotonin transporter than methamphetamine.

涉及多巴胺能、谷氨酸能和血清素能神经递质系统的神经元适应负责行为致敏。由于共同的潜在机制，可以观察到不同药物类别的化合物之间的交叉敏感性。本研究的目的是确定 RU 24969（一种 5-HT _1A/1B受体激动剂）会在雄性和雌性断奶前大鼠中与可卡因或甲基苯丙胺相互交叉敏感。大鼠用 RU 24969（0 或 5 mg/kg）预处理 4 天（PD 17-20），然后在 PD 22 用可卡因（10 或 20 mg/kg）或甲基苯丙胺（1 或 2 mg/kg）攻击。还评估了相互交叉致敏性（即，用精神兴奋剂对大鼠进行预处理并用 RU 24969 进行测试）。在后续实验中，使用为期一天的预处理方案评估了 RU 24969 和可卡因相互交叉致敏的能力。可卡因和 RU 24969 之间的相互交叉致敏作用在断奶前大鼠中很明显，而甲基苯丙胺和 RU 24969 没有交叉致敏作用。当使用单试验预处理方案时，仅当大鼠用 RU 24969 预处理并用可卡因测试时才检测到交叉致敏作用，但反之则没有。总之，目前的结果表明，非选择性 5-HT_1A/1B受体激动剂 RU 24969 在断奶前大鼠中与可卡因交叉敏感，但不与甲基苯丙胺交叉敏感。这种二分法可能是可卡因对血清素转运蛋白的亲和力高于甲基苯丙胺的功能。