Intracranial Drug Self-administration

颅内药物自我给药

• 批准号: 8736723
• 负责人: SATOSHI IKEMOTO
• 金额: $ 47.79万
• 依托单位: NATIONAL INSTITUTE ON DRUG ABUSE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8736723
• 关键词: Affect; Amphetamines; Brain; Brain region; Chemicals; Chronic; Cognitive; Communication; Disease; Dose; Drug Addiction; Drug usage; Esthesia; Food; Food deprivation (experimental); Goals; Hour; Injection of therapeutic agent; Intraperitoneal Injections; Lead; Length; Light; Microinjections; Moods; Motivation; Motor; Motor Activity; Neurons; Neurotransmitters; Obsessive-Compulsive Disorder; Performance; Pharmaceutical Preparations; Procedures; Process; Psyche structure; Psychological reinforcement; Rattus; Rewards; Saline; Self Administration; Sensory; Stress; System; Techniques; Testing; Time; Weight; addiction; alertness; brain cell; chemical release; drug of abuse; effective therapy; food restriction; intraperitoneal; neuromechanism; preference; visual stimulus

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.

众所周知，安非他明可以提高警觉性、情绪、动力和运动能力。安非他明的长期使用与成瘾和精神疾病有关，包括情绪、精神病、强迫症和强迫症。安非他明的这些已知效应可能表明，安非他明的使用改变了将感觉信息整合为行动的动机和认知过程。为了研究达非他明对这种整合过程的影响，我们采用了非条件性视觉刺激的感觉寻求。具体地说，我们的程序要求大鼠杠杆按压以获得闪光，这在大鼠身上是弱强化的。由于苯丙胺对药物寻找和精神状态的影响可因应激而加剧，因此我们还考察了慢性限食引起的应激及其与苯丙胺的相互作用对VS寻找的影响。 我们发现，在慢性食物限制(FR)大鼠(体重的85-90%)上，腹腔注射1 mg/kg苯丙胺(IP)显著增加VS增强的杠杆压力，而0.3 mg/kg剂量没有可靠的作用，而3 mg/kg剂量可靠地减少了寻找。在这些实验中，FR大鼠的运动活动受到的影响与寻找相比略有不同：1 mg/kg剂量增加了运动活动，3 mg/kg剂量增加更多。与FR大鼠不同的是，给予随意(AD)食物的大鼠在接受这些剂量的苯丙胺治疗时并没有可靠地增加寻找的次数，同时显著增加了运动活动。 我们还考察了食物限制的长度对苯丙胺诱导的VS搜索的影响。安非他明注射(1 mg/kg)24小时或3天或7天的食物剥夺与寻找相比没有增加，而2周的食物剥夺与寻找相比显著增加，提示需要慢性食物限制才能增加苯丙胺对寻找的影响。 我们还检查了重复注射苯丙胺(1 mg/kg，ip)后3周孵育的效果(在2周内重复注射8次)。当孵育后给予0.1~1 mg/kg的苯丙胺时，预先暴露苯丙胺对FR或AD大鼠的VS寻找无明显影响，但对运动活动有敏化作用。然而，整个过程包括重复注射(生理盐水或苯丙胺)，然后孵育3周，使FR大鼠对苯丙胺对VS寻找的影响更加敏感。在不使用安非他明的情况下，FR大鼠与AD大鼠相比无明显差异，但有生理盐水或安非他明暴露史的FR大鼠较安非他明0.3 mg/kg或1 mg/kg处理的FR大鼠显著增加。 综上所述，这些结果表明，食物限制是苯丙胺诱导的VS寻找的一个重要因素，但不是运动活动的一个重要因素。苯丙胺调节的促进VS寻找的神经机制可能与运动活动的神经机制有本质上的不同。

项目成果

Mapping of reinforcing and analgesic effects of the mu opioid agonist endomorphin-1 in the ventral midbrain of the rat.

• DOI: 10.1007/s00213-012-2753-6
• 发表时间: 2012-11
• 期刊: PSYCHOPHARMACOLOGY
• 影响因子: 3.4
• 作者: Jhou, Thomas C.;Xu, Sheng-Ping;Lee, Mary R.;Gallen, Courtney L.;Ikemoto, Satoshi
• 通讯作者: Ikemoto, Satoshi

Synergistic interaction between baclofen administration into the median raphe nucleus and inconsequential visual stimuli on investigatory behavior of rats.

• DOI: 10.1007/s00213-011-2450-x
• 发表时间: 2012-03
• 期刊: PSYCHOPHARMACOLOGY
• 影响因子: 3.4
• 作者: Vollrath-Smith, Fiori R.;Shin, Rick;Ikemoto, Satoshi
• 通讯作者: Ikemoto, Satoshi

The GABAB receptor agonist baclofen administered into the median and dorsal raphe nuclei is rewarding as shown by intracranial self-administration and conditioned place preference in rats.

• DOI: 10.1007/s00213-009-1757-3
• 发表时间: 2010-03
• 期刊: PSYCHOPHARMACOLOGY
• 影响因子: 3.4
• 作者: Shin, Rick;Ikemoto, Satoshi
• 通讯作者: Ikemoto, Satoshi

Rewarding and incentive motivational effects of excitatory amino acid receptor antagonists into the median raphe and adjacent regions of the rat.

兴奋性氨基酸受体拮抗剂的奖励和激励动机作用进入大鼠的中间区域和相邻区域。

• DOI: 10.1007/s00213-012-2759-0
• 发表时间: 2012-12
• 期刊: PSYCHOPHARMACOLOGY
• 影响因子: 3.4
• 作者: Webb, Sierra M.;Vollrath-Smith, Fiori R.;Shin, Rick;Jhou, Thomas C.;Xu, Shengping;Ikemoto, Satoshi
• 通讯作者: Ikemoto, Satoshi

Brain reward circuitry beyond the mesolimbic dopamine system: a neurobiological theory.

• DOI: 10.1016/j.neubiorev.2010.02.001
• 发表时间: 2010-11
• 期刊: NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
• 影响因子: 8.2
• 作者: Ikemoto, Satoshi