Research Article • DOI: 10.2478/s13380-013-0146-x • Translational Neuroscience • 4(4) • 2013 • 419-428 Translational Neuroscience THE EFFECT OF NUCLEUS Yarong Wang#1, Jia Zhu#1, ACCUMBENS LESIONS ON Ling Chen2, Yijun Liu3, Qiang Li1, APPETITE, SEXUAL FUNCTION, Weichuan Yang1, Wei Li1, AND NICOTINE DEPENDENCE IN Liyan Zhao4, Mark S. Gold3, Jifeng Sun5*, RECOVERING HEROIN ADDICTS Wei Wang1* Abstract 1 Department of Radiology, Tangdu Hospital, The nucleus accumbens (NAc) is a key part of the neural circuitry that creates reward, pleasure and motivation the Fourth Military Medical University, 569 that facilitates human feeding, sexual and smoking behaviors. In the brain reward system, the NAc is a crucial Xinsi Road, Baqiao District, Xi’an 710038, component responsible for natural and drug-induced reinforcement behaviors. Yet it is unclear whether NAc is China. indispensible for all reward behaviors in human beings. The present study aimed to investigate the long-term 2 Department of Oncology, the First effects of NAc ablation on sexual function, appetite, and nicotine dependence level in chronic heroin users. Aliated Hospital of Xi’an Jiaotong Eighteen former heroin–dependent patients (male) with bilateral NAc ablation via stereotactic radiofrequency University, 766 West Yantan Road, Xi’an surgery for alleviating drug psychological dependence were recruited. Their postoperative time ranged from 12 710061, China. to 103 months. All subjects received MRI scans for assessing the accuracy of the lesion site. Evaluation of appetite, 3 Department of Psychiatry, University of sexual function, and nicotine dependence were measured using the Simplified Nutrition Appetite Questionnaire, Florida College of Medicine, 100 Newell Dr the Brief Sexual Function Inventory, and the Fagerström Test for Nicotine Dependence, respectively. After L4100, Gainesville, Florida 32610, USA. precluding the potential confounding variables, such as drug use (dosage and duration), post-operation 4 National Institute on Drug Dependence, duration, age, body-weight, marital status and education level, ANOVA with repeated measures revealed that Peking University, 38 Xueyuan Road, the NAc ablation improved the patients’ appetite, sexual drive and sexual satisfaction. Yet there was no change in Beijing 100083, China. male erectile function, ejaculatory function, or nicotine dependence levels compared to the preoperative. These 5 Department of Nephrology, Tangdu may suggest that although NAc is a key part of the neural circuitry, the NAc surgical lesions left the fundamental Hospital, the Fourth Military Medical aspects of natural and drug-induced reinforcement and motivation almost intact. University, 569 Xinsi Road, Baqiao District, Keywords Xi’an 710038, China. • Nucleus accumbens (NAc) • Heroin dependence • Human reward behavior Received 18 July 2013 accepted 02 December 2013 © Versita Sp. z o.o. Introduction conditioning [12], so it is of great significance to in the reinforcing action of primary reinforcers explore the relationship between the NAc and and illicit drugs. In human and animal brains there exists a specific human reward behaviors. To investigate the functional role of NAc reward mechanism that serves to maintain In this system, especially in the NAc, in human reward behaviors, scholars have and encourage the motivations and activities dopamine (DA) predominantly mediates the employed multiple approaches, including beneficial for survival and reproduction. primary reinforcing characteristics of natural neuroanatomical [22], electrophysiological The neural substrate underlying the reward rewards (such as food and sex), in addition to [23], intracranial microinjection [24] and mechanism is mainly based on the meso- those of drug abuse and addiction [13]. When a neuroimaging methods [25]. The intracranial corticolimbic dopaminergic pathway that natural reinforcer or drug of abuse is consumed, microinjection can identify neural circuitry and originates in the midbrain ventral tegmental extracellular DA concentration in the NAc is explore the reward effects of multiple chemical area (VTA) with projections to the nucleus increased, which is associated with the feeling transmitters, but cannot directly analyze the accumbens (NAc) and connections with other of “euphoria” [13-15]. When anticipating or neural transmission involved in humans [24]. brain regions, including the amygdala, ventral actually consuming the reinforcer [13,16,17] Functional neuroimaging is a powerful tool to pallidum, dorsal striatum, hippocampus and or when activated to encode saliency of a reveal the brain regions associated with reward prefrontal cortex [1]. Ample evidence confirms given stimulant [17-20], the NAc can also responses [25], but it cannot determine which that almost all drugs of abuse (heroin, cocaine, release DA, facilitating the reward behaviors. brain area is essential for reward behavior. morphine, amphetamine) may dysregulate this It is noteworthy that a natural reinforcer Studies of patients with NAc lesions are system, inducing the development of addiction differs from drugs of abuse in reinforcing unique in enabling us to examine the specific [2-6]. Further, natural reward and drug abuse action. The primary difference lies in that the NAc-behavior relationships [22]. To date, few share this neural circuitry to accomplish the latter can modify the kinetics and amplitude studies have explored the effects of NAc lesions reinforcement effects [7-11]. In this neural of the dopamine release and form memories on reward behavior in humans. The most circuitry NAc plays an important role in associated with drug consumption [21]. Such notable to mention are a case study [26] and reward/saliency, motivation/drive, memory/ evidence shows that the NAc has a pivotal role two studies in which NAc lesions extensively * E-mail: [email protected] ; [email protected] # These two authors contributed to this work equally. 419 Translational Neuroscience involved adjacent brain structures [27,28]. daily methadone dose. All the participants were The post-surgery follow-up was regularly The lack of literature on specific NAc lesions required to have a urine toxicology screening conducted via telephone after a 6-month makes it difficult to do a clinical-pathological test at the time of study enrollment. interval. Our investigators focused on the correlation analysis to human NAc lesions. Exclusion criteria included: a) incorrect patients’ physical, psychological, neurological The objective of this study was to better NAc target site or lesions that involved an and psychiatric information, especially their understand the structure-function relationship adjacent brain structure according to the MRI illicit drug use. These data were obtained of the NAc by identifying the relations between data (see “Accuracy assessment of ablation via patient self-report or the report of their the NAc and specific reward behaviors in a site”); b) current or past psychiatric illness families living with them. When the patients group of patients who underwent bilateral NAc other than heroin dependence; c) neurological encountered any health problem and sought ablation by stereotactic surgery for alleviating signs, severe mental disorder, or intelligence further medical treatment, physical and opiate drug psychological dependence. dysfunction; d) current medical illness; e) imaging examinations were available. After a Specifically, we investigated the long-term dependence on any other psychoactive period (1~7 years), there were 22 patients lost inuence of bilateral NAc ablation on natural substance other than nicotine or coffee; f) to follow up. Among the remaining 20 patients, reward (appetite, sexual behavior) and drug history of head trauma; and g) MRI examination 19 had no MRI scan contraindication and were reward (nicotine dependence) in these patients. contraindication. None of the participants willing to take part in the present study. experienced strong withdrawal symptoms All telephone interviews were conducted Materials and methods during the study. 1 participant was excluded by 3 highly experienced interviewers in social because the brain structure MRI scan revealed and psychiatric research. The telephone The ethics statement and study that his NAc lesions involved an adjacent conversation was recorded during the population structure. Eventually, 18 participants entered telephone interview. And at least half of the live This study followed the principles outlined in the next analyses. conversations were monitored in real time by a the Declaration of Helsinki (6th revised version, supervisor to ensure the reliability and validity Edinburgh, 2000). Ethics approval was obtained Background of the study population of survey data. from the Ethics Committee of the Fourth and their follow-up investigation Military Medical University (at the Review From 2002 to 2008, a clinical study was Experimental procedures Board Meeting held on 18th March 2002) and conducted to explore a new way to alleviate Tangdu Hospital Ethic Committee (approval opiate drug psychological dependence by All participants were well informed about the no. TDLL-2009039 from 5th March 2009). The ablating the NAc with stereotactic surgery in study and gave their consents to the surgical authors declare no conflict of interest. China [29]. There were a total of 42 intractable treatment, the post-surgery MRI scan for Nineteen of 42 male chronic heroin heroin dependent patients who underwent verifying the lesion loci and the questionnaire