Behavioral Neuroscience Branch, National Institute on Drug Abuse, National Institutes of Health, US Department of Health and Human Services, Baltimore, MD 21224, USA.
Psychopharmacology (Berl). 2012 Mar;220(1):15-25. doi: 10.1007/s00213-011-2450-x. Epub 2011 Sep 9.
Noncontingent administration of amphetamine into the ventral striatum or systemic nicotine increases responses rewarded by inconsequential visual stimuli. When these drugs are contingently administered, rats learn to self-administer them. We recently found that rats self-administer the GABA(B) receptor agonist baclofen into the median (MR) or dorsal (DR) raphe nuclei.
We examined whether noncontingent administration of baclofen into the MR or DR increases rats' investigatory behavior rewarded by a flash of light.
Contingent presentations of a flash of light slightly increased lever presses. Whereas noncontingent administration of baclofen into the MR or DR did not reliably increase lever presses in the absence of visual stimulus reward, the same manipulation markedly increased lever presses rewarded by the visual stimulus. Heightened locomotor activity induced by intraperitoneal injections of amphetamine (3 mg/kg) failed to concur with increased lever pressing for the visual stimulus. These results indicate that the observed enhancement of visual stimulus seeking is distinct from an enhancement of general locomotor activity. Visual stimulus seeking decreased when baclofen was co-administered with the GABA(B) receptor antagonist, SCH 50911, confirming the involvement of local GABA(B) receptors. Seeking for visual stimulus also abated when baclofen administration was preceded by intraperitoneal injections of the dopamine antagonist, SCH 23390 (0.025 mg/kg), suggesting enhanced visual stimulus seeking depends on intact dopamine signals.
Baclofen administration into the MR or DR increased investigatory behavior induced by visual stimuli. Stimulation of GABA(B) receptors in the MR and DR appears to disinhibit the motivational process involving stimulus-approach responses.
非条件给予安非他命到腹侧纹状体或全身尼古丁会增加对无关视觉刺激的奖励反应。当这些药物被条件给予时,老鼠会学会自我给药。我们最近发现,老鼠将 GABA(B)受体激动剂巴氯芬自我给药到中缝(MR)或背侧(DR)中缝核。
我们检查了非条件给予巴氯芬到 MR 或 DR 是否会增加老鼠对光闪烁的探索行为的奖励。
条件呈现光闪烁略微增加了压杆次数。虽然非条件给予巴氯芬到 MR 或 DR 并不能可靠地增加在没有视觉刺激奖励的情况下的压杆次数,但相同的操作明显增加了视觉刺激奖励的压杆次数。腹腔注射安非他命(3 毫克/千克)引起的运动活动增加并没有与视觉刺激的压杆次数增加同时发生。这些结果表明,观察到的视觉刺激寻求的增强与一般运动活动的增强不同。当巴氯芬与 GABA(B)受体拮抗剂 SCH 50911 共同给予时,视觉刺激的寻求减少,证实了局部 GABA(B)受体的参与。当巴氯芬给药之前腹腔注射多巴胺拮抗剂 SCH 23390(0.025 毫克/千克)时,寻求视觉刺激也减弱,表明增强的视觉刺激寻求取决于完整的多巴胺信号。
MR 或 DR 中的巴氯芬给药增加了视觉刺激诱导的探索行为。MR 和 DR 中的 GABA(B)受体刺激似乎抑制了涉及刺激接近反应的动机过程。