Functional and anatomical evidence for different dopamine dynamics in the core and shell of the nucleus accumbens in slices of rat brain

The characteristics of dopamine (DA) uptake and release were compared in the core and shell of the nucleus accumbens (NAc). DA release was elicited from rat brain slices by local electrical stimulation, and its extracellular concentration was monitored with fast-scan cyclic voltammetry using Nafion-coated, carbon-fiber microelectrodes. The voltammetric results show that the values of DA release and uptake in the shell NAc are approximately one-third of those measured in the core region, and DA uptake in the shell was less sensitive than the core to inhibition by either cocaine or nomifensine. The density of [³H]mazindol binding sites in the NAc was examined by autoradiography and the shell was found to have an average of half the number of DA uptake sites measured in the core region. This combination of anatomical and functional results shows that DA neurotransmission in the shell NAc is distinct from that in the core region. These data are consistent with the view that multiple functional forms of the DA transporter, exhibiting disparate kinetics and pharmacology, exist in different brain regions that exhibit disparate kinetics and pharmacology. Different forms of the transporter, combined with different release kinetics and auto- and heteroreceptor activity, give a vast range of possibilities for regional variation in DA neurotransmission. © 1996 Wiley-Liss, Inc.     

固定比率食物强化法建立大鼠可卡因药物辨别模型

目的 建立固定比率为10(FR10)的大鼠可卡因药物辨别模型,进行可卡因辨别效应和剂量关系的测试及半数有效量(ED50)测定.方法 采用FR值逐渐递增1和每获得5次奖励FR值自动增加1的两种实验程序对32只SD大鼠进行食物训练,食物训练成功的大鼠给予可卡因10 mg·kg-1或氯化钠注射液进行辨别训练;将辨别训练成功的...     

蛋白-蛋白相互作用调节多巴胺受体D3的功能(英文)

Gαi/o蛋白偶联的多巴胺受体D3在包括付隔核的边缘系统中丰富表达。其不仅能调节边缘系统功能,而且在神经精神疾病和神经退行性病变过程中起重要作用。D3受体的胞内结构,尤其是第三个细胞内环和C末端,可以和多个靠近细胞内膜的蛋白相互结合,以此来调控受体的膜表面表达及其功效。最近的研究发现,D3受体和蛋白激酶能够以此模型相互结合。突触富集的钙/钙调蛋白依赖的蛋白激酶II(CaMKII)直接与D3受体第三个细胞内环的N末端结合。这种结合是钙离子依赖的,并被CaMKII激酶的自我磷酸化所加强。在大鼠的付隔核神经元中,钙离子水平的升高能诱导CaMKII与D3结合,并磷酸化D3受体上特定的丝氨酸位点。CaMKII介导的受体磷酸化能抑制受体的功能,进而调节动物对可卡因兴奋剂的行为学反应。这些结果揭示了G蛋白偶联受体与CaMKII作用的一种新模式。蛋白间动态的结合使得D3受体的膜表达丰度、衰减周期和功能受到多种信号和酶蛋白的调节。     

Cue-elicited cocaine craving and autogenic relaxation : Association with treatment outcome

Prior to entering a pharmacotheraphy trial for the treatment of cocaine dependence, 19 patients participated in a pretreatment cue-reactivity protocol that concluded with a relaxation exercise. Measures included self-reported craving and skin conductance level (SCL). Post hoc exploratory analyses suggest that neither craving nor change in SCL in response to cocaine cues differentiated patients who subsequently achieved abstinence from those who did not. Craving following the relaxation procedure did differentiate the two groups: patients who subsequently initiated abstinence in treatment reported a reduction in cue-elicited craving to below baseline levels; craving reported by patients who did not successfully complete treatment remained elevated.     

The formation of cocaethylene and clinical presentation of ED patients testing positive for the use of cocaine and ethanol

The purpose of this investigation was to document the clinical presentation of emergency department (ED) patients who tested positive for concurrent cocaine (COC) and ethanol (EtOH) use and the incidence of cocaethylene (CE) formation in this study population. Four study groups were evaluated: (1) drug-free, (2) EtOH-only, (3) COC-only, and (4) COC plus EtOH. CE was detected in plasma or urine specimens in 88% of the COC/EtOH-positive patients, and correlated directly with plasma COC and its metabolite benzoylecognine. Blood pressure and body temperature did not vary across study groups. COC/EtOH-positive patients displayed a significantly higher mean respiratory rate while the EtOH-only study group had an elevated mean heart rate. No significant differences were detected with respect to cardiac and neurological complaints between study groups. Trauma complaints in the drug-positive groups were more frequent than the incidence reported in the drug-free population. COC/EtOH-positive patients had the greatest percentage of trauma complaints (34.6%). Nearly half of the patients who tested positive for CE cited trauma as the primary reason for reporting to the ED. We conclude that ED patients who have concurrently used COC and EtOH are more closely associated with presentations related to traumatic injury than to those related to toxicologic complications.     

Association Among Periodontitis and the Use of Crack Cocaine and Other Illicit Drugs

Background: Crack cocaine can alter functions related to the immune system and exert a negative influence on progression and severity of periodontitis. The aim of this study is to compare periodontal status between crack cocaine users and crack cocaine non‐users and investigate the association between crack cocaine and periodontitis after adjustments for confounding variables. Methods: This cross‐sectional study evaluated 106 individuals exposed to crack cocaine and 106 never exposed, matched for age, sex, and tobacco use. An examiner determined visible plaque index (VPI), marginal bleeding index, supragingival dental calculus, probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BOP). Logistic regression was used to model associations between crack cocaine and periodontitis (at least three sites with CAL >4 mm and at least two sites with PD >3 mm, not in the same site or tooth). Results: Prevalence of periodontitis among crack non‐users and crack users was 20.8% and 43.4%, respectively. Crack users had greater VPI, BOP, PD ≥3 mm, and CAL ≥4 mm than crack non‐users. Periodontitis was associated with age >24 years, schooling ≤8 years, smoking, moderate/heavy alcohol use, and plaque rate ≥41%. Crack users had an approximately three‐fold greater chance (odds ratio: 3.44; 95% confidence interval: 1.51 to 7.86) of periodontitis than non‐users. Conclusion: Occurrence of periodontitis, visible plaque, and gingival bleeding was significantly higher among crack users, and crack use was associated with occurrence of periodontitis.     

Inhibition of serotonin uptake by synaptosomes and glial cells induced by certain drugs

Uptake of [¹⁴C]serotonin by glial cells and synaptosomes in the rabbit cerebral cortex was studied. The value of K_m for serotonin uptake was the same (0.083±0.02 M) for both synaptosomes and glial cells. Cortical synaptosomes took up serotonin twice as fast as glial cells (the rates of uptake were compared as protein). Of the psychotropic drugs tested, the most active inhibitors of both synaptosomal and glial serotonin uptake were the tricyclic antidepressant imipramine and the psychostimulant cocaine which, in concentrations of 50 M, inhibited uptake of [¹⁴C]serotonin in synaptosomes by 90% and in glial cells by 75–80%.Laboratory of Neurochemical Pharmacology, Institute of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. Department of Biochemistry, Tbilisi University. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 11, pp. 564–566, November, 1979.     

Percutaneous interventions in patients with cocaine-associated myocardial infarction: a case series and review.

Cocaine-associated myocardial infarction (CAMI) is a well-reported entity. Most previous reports on CAMI have been limited to conservative care utilizing benzodiazepines, aspirin, nitroglycerin, calcium channel blockers, and thrombolytics. Current guidelines on CAMI advocate immediate use of angiography and angioplasty if available rather than routine administration of thrombolytics. However, based on literature search from 1966 to 2001 (using keywords "cocaine," "myocardial infarction," and "angioplasty"), there have been only two case reports of percutaneous coronary intervention (PCI) in patients with cocaine-associated myocardial infarction. Both were notable for complications either during or immediately after the procedure. We report a series of 10 patients with cocaine-associated myocardial infarction who were treated with percutaneous interventions, which included angioplasty, stenting, and AngioJet mechanical extraction of thrombus. Despite the different arteriopathic process involved, our findings suggest that PCI can be performed safely and with a high degree of procedural success in patients with CAMI.