Department of Psychology, Arizona State University, Tempe, AZ 85287, USA.
Psychopharmacology (Berl). 2011 Feb;213(2-3):307-20. doi: 10.1007/s00213-010-2071-9. Epub 2010 Nov 16.
The action of serotonin (5-HT) at the 5-HT(2A) receptor subtype is thought to be involved in cocaine-seeking behavior that is motivated by exposure to drug-associated cues and drug priming. 5-HT(2A) receptors are densely clustered in the ventromedial prefrontal cortex (vmPFC), an area that plays a role in mediating cocaine-seeking behavior.
This study examined the hypothesis that M100907, a 5-HT(2A) receptor antagonist, infused directly in the vmPFC attenuates cue- and cocaine-primed reinstatement of cocaine-seeking behavior.
Rats trained to self-administer cocaine (0.75 mg/kg, i.v.) paired with light and tone cues underwent extinction training during which operant responses produced no consequences. Once behavior extinguished, rats were tested for reinstatement of responding elicited by either response-contingent presentations of the cocaine-paired light/tone cues or by cocaine-priming injections (10 mg/kg, i.p.) within 1 min after pretreatment with microinfusions of M100907 (0.1, 0.3, 1.0, or 1.5 μg/0.2 μl/side) into the vmPFC.
Intra-vmPFC M100907 decreased cue-elicited reinstatement at the two highest doses (1.0 and 1.5 μg) but produced only a slight decrease in cocaine-primed reinstatement that was not dose dependent. The decrease in cue reinstatement was not likely due to impaired ability to respond since intra-vmPFC M100907 infusions had minimal effect on cocaine self-administration and no effect on cue-elicited sucrose-seeking behavior, or spontaneous or cocaine-induced locomotion. M100907 infusions into the adjacent anterior cingulate cortex had no effect on cue reinstatement.
The results suggest that the blockade of 5-HT(2A) receptors in the vmPFC selectively attenuates the incentive motivational effects of cocaine-paired cues.
血清素（5-HT）在 5-HT（2A）受体亚型上的作用被认为与可卡因寻求行为有关，这种行为是由暴露于药物相关线索和药物引发引起的。5-HT（2A）受体在腹内侧前额叶皮层（vmPFC）中密集聚集，该区域在介导可卡因寻求行为中起作用。
本研究检验了这样一个假设，即 5-HT（2A）受体拮抗剂 M100907 直接输注到 vmPFC 会减弱线索和可卡因引发的可卡因寻求行为的复燃。
接受可卡因（0.75mg/kg，iv）与光和声线索配对的自我给药训练的大鼠接受了消退训练，在此期间，操作性反应没有产生任何后果。一旦行为消退，通过以下方式测试大鼠对可卡因配对的光/声线索的条件反应性呈现或可卡因引发的注射（10mg/kg，ip）的反应复燃：在预处理后 1 分钟内进行 vmPFC 中的微输注M100907（0.1、0.3、1.0 或 1.5μg/0.2μl/侧）。
vmPFC 内的 M100907 降低了两个最高剂量（1.0 和 1.5μg）的线索引发的复燃，但可卡因引发的复燃仅略有减少，且无剂量依赖性。线索复燃的减少不太可能是由于反应能力受损所致，因为 vmPFC 内的 M100907 输注对可卡因自我给药几乎没有影响，也不会影响线索引发的蔗糖寻求行为，或自发或可卡因引起的运动。M100907 输注到相邻的前扣带皮层对线索复燃没有影响。
结果表明，vmPFC 中 5-HT（2A）受体的阻断选择性地减弱了可卡因配对线索的激励动机效应。
