Intracranial Drug Self-administration

已知安非他明可增强警觉性、情绪、动力和运动表现。长期使用安非他明与成瘾和精神状况有关，包括情绪、精神病、强迫症和强迫症。这些已知的安非他明的影响可能表明，安非他明管理改变动机和认知过程，整合感官信息的行动。为了研究达非他明对这种整合过程的影响，我们采用了非条件视觉刺激（VS）的感觉寻求。 具体来说，我们的程序要求大鼠按压以获得闪光，这在大鼠中是微弱的强化。 由于安非他明对药物寻求和精神状况的影响可能会因压力而加剧，我们还研究了慢性食物限制引起的压力及其与安非他明对VS寻求的相互作用的影响。 我们发现，在长期食物限制（FR）大鼠（85-90%的原始重量），腹膜内（IP）注射1毫克/公斤安非他明显着增加了由VS增强的压迫，而0.3毫克/公斤剂量没有可靠的效果，3毫克/公斤剂量可靠地减少VS寻求。在这些测试中，FR大鼠的自发活动受到的影响与VS寻求略有不同：1 mg/kg剂量增加自发活动，3 mg/kg剂量增加更多。与FR大鼠不同，大鼠随意（AD）获得食物并没有可靠地增加VS寻求这些剂量的安非他明治疗时，同时显着增加自发活动。 我们还研究了食物限制的长度对苯丙胺诱导的VS寻求的影响。禁食24小时或禁食3天或7天并注射安非他明（1 mg/kg）并没有增加VS寻求，而2周的FR显著增加VS寻求，这表明安非他明需要长期的食物限制来增加VS寻求。 我们还检查了重复注射（2周内8次）安非他明（1 mg/kg，IP），然后孵育3周的效果。在孵育后用0.1-1 mg/kg安非他明激发时，先前安非他明暴露对FR或AD大鼠的VS寻求没有明显影响，但对自发活动有敏化作用。然而，整个过程包括重复注射（生理盐水或安非他明），然后进行3周的孵育，使FR大鼠更敏感的安非他明对VS寻求的影响。虽然FR大鼠在无苯丙胺的VS寻求中与AD大鼠没有差异，但先前暴露于盐水或苯丙胺的FR大鼠在0.3或1 mg/kg苯丙胺的治疗下显著增加了VS寻求。 总之，这些结果表明，食物限制是一个重要的因素，在安非他明诱导的VS寻求，但不是在自发活动。安非他明调节以促进VS寻求的神经机制可能与自发活动的神经机制有很大不同。

Amphetamines are known to enhance alertness, mood, motivation and motor performance. Chronic use of amphetamines is associated with addiction and mental conditions including mood, psychotic, obsessive and compulsive disorders. These known effects of amphetamines may suggest that amphetamine administration alters motivational and cognitive processes that integrate sensory information for action. To study effects of damphetamine on such integrative processes, we employed sensation seeking of unconditioned visual stimuli (VS). Specifically, our procedure required rats to lever-press to obtain a flash of light, which is weakly reinforcing in rats. Because amphetamines effects on drug seeking and mental conditions can be exacerbated by stress, we also examined effects of stress induced by chronic food-restriction and its interaction with amphetamine on VS seeking. We found that in chronically food-restricted (FR) rats (85-90% of their original weights), intraperitoneal (IP) injections of 1 mg/kg amphetamine markedly increased lever-pressing reinforced by VS, while the 0.3-mg/kg dose had no reliable effect, and the 3-mg/kg dose reliably decreased VS seeking. Locomotor activity of FR rats during these tests was affected somewhat differently than VS seeking: The 1-mg/kg dose increased locomotor activity, and the 3-mg/kg dose increased it even more. Unlike FR rats, rats that were given ad libitum (AD) access to food did not reliably increase VS seeking when treated with these doses of amphetamine, while significantly increasing locomotor activity. We also examine effects of the length of food restriction on amphetamine-induced VS seeking. Food deprivation of 24 hours or FR of 3 or 7 days with amphetamine injections (1mg/kg) did not increase VS seeking , while a 2 week FR significantly increased VS seeking, suggesting that chronic food restriction is needed for amphetamine to increase VS seeking. We also examined effects of repeated injections (8 times over 2 weeks) of amphetamine (1 mg/kg, IP) followed by a 3-week incubation. When challenged with 0.1-1 mg/kg amphetamine after incubation, prior amphetamine exposure did not have clear effects on VS seeking in FR or AD rats, but had sensitizing effects on locomotor activity. However, the whole procedure consisting of repeated injections (either saline or amphetamine) followed by a 3-week incubation made FR rats more sensitive to the effects of amphetamine on VS seeking. While FR rats were not different from AD rats in VS seeking without amphetamine, FR rats with prior saline- or amphetamineexposure significantly increased VS seeking with treatments of 0.3 or 1 mg/kg amphetamine. In summary, these results suggest that food restriction is an importnat factor in amphetamine-induced VS seeking, but not in locomotor activity. Neural mechanisms that amphetamine modulates to facilitate VS seeking may be substantially different from those of locomotor activity.