Fletcher P J, Korth K M
Department of Psychology, University of Toronto, Ontario, Canada.
Psychopharmacology (Berl). 1999 Feb;142(2):165-74. doi: 10.1007/s002130050876.
Previously, we have demonstrated that 5-hydroxytryptamine (5-HT) injected into the nucleus accumbens attenuates the potentiating effects of d-amphetamine on responding for conditioned reward (CR). The present studies examined the 5-HT receptor involved in this effect by investigating the effects of 5-HT agonists with differing affinities for 5-HT1 and 5-HT2 receptors on d-amphetamine-induced potentiation of responding for CR. Rats were trained to associate a light/tone stimulus (subsequently the CR) with water delivery. In a test phase, they were allowed access to a lever delivering the CR, and an inactive (NCR) lever. Responding on the CR lever was greater than responding on the NCR lever, indicating that the light/tone stimulus functioned as a CR. Responding for the CR was selectively potentiated by injections of d-amphetamine (10 microg) into the nucleus accumbens. This effect was reduced by injections into the nucleus accumbens of 5-CT (0.5 and 1 microg), RU24969 (10 microg), CP93,129 (1.25 and 2.5 microg) but not by DOI (10 microg) or 8-OH-DPAT (5 microg). The lower doses of 5-CT and CP93,129 did not reduce baseline responding for CR, or responding for water in a separate group of animals, indicating that the effects of these drugs were behaviourally selective. The higher doses abolished the CR effect, and in the case of 5-CT and RU24969 also reduced responding for water. All of the effective drugs share in common the ability to stimulate 5-HT1B receptors, albeit with differing selectivities. The effect of CP93,129, the most selective of the 5-HT1B agonists, to inhibit the response-potentiating effect of d-amphetamine was reversed by the 5-HT(1B/1D) antagonist GR127935 (3 mg/kg). The results indicate that activation of 5-HT1B receptors within the nucleus accumbens attenuates the effects of a dopamine-dependent behaviour, and that activation of these receptors can oppose the behavioural effects of elevated mesolimbic dopamine transmission.
此前，我们已经证明，向伏隔核注射5-羟色胺（5-HT）可减弱右旋苯丙胺对条件性奖赏（CR）反应的增强作用。本研究通过研究对5-HT1和5-HT2受体具有不同亲和力的5-HT激动剂对右旋苯丙胺诱导的CR反应增强作用的影响，来考察参与此效应的5-HT受体。大鼠经训练使光/音刺激（随后为CR）与水的递送相关联。在测试阶段，让它们能够接触到一个递送CR的杠杆和一个无效（NCR）杠杆。对CR杠杆的反应大于对NCR杠杆的反应，表明光/音刺激起到了CR的作用。向伏隔核注射右旋苯丙胺（10微克）可选择性地增强对CR的反应。向伏隔核注射5-CT（0.5和1微克）、RU24969（10微克）、CP93,129（1.25和2.5微克）可减弱此效应，但注射DOI（10微克）或8-OH-DPAT（5微克）则无此作用。较低剂量的5-CT和CP93,129并未降低另一组动物对CR的基线反应或对水的反应，表明这些药物的作用具有行为选择性。较高剂量消除了CR效应，就5-CT和RU24969而言，还降低了对水的反应。所有有效药物都具有刺激5-HT1B受体的能力，尽管选择性不同。5-HT（1B/1D）拮抗剂GR127935（3毫克/千克）可逆转5-HT1B激动剂中选择性最高的CP93,129抑制右旋苯丙胺反应增强作用的效应。结果表明，伏隔核内5-HT1B受体的激活减弱了多巴胺依赖性行为的效应，并且这些受体的激活可对抗中脑边缘多巴胺传递升高的行为效应。
