Drug history modifies the behavioral effects of pentobarbital

Behavior of squirrel monkeys, maintained by the termination of stimuli associated with electric shock, was suppressed by response-dependent shock delivery. The effects of pentobarbital on this behavior depended on whether monkeys had previously received morphine. In monkeys without experience with drugs, pentobarbital increased responding. In monkeys with recent experience with morphine, however, pentobarbital resulted in a smaller increase or decrease in responding. The rate-decreasing effects of pentobarbital after a history of morphine administration could be reversed by the administration of d-amphetamine. These findings suggest that the behavioral effects of abused drugs may depend on previous experience with other drugs, even when those drugs are from a different pharmacological class.     

Morphine tolerance and dependence induced by intraventricular injection

Injection of small quantities of morphine into the cerebral ventricular system of awake, relatively unrestrained, monkeys depressed or abolished operant food-reinforced lever pressing. After repeated injections progressively higher doses of morphine were needed to depress responding. Also, dependence could be demonstrated in these animals by precipitating specific abstinence signs with an antagonist.     

Morphine: conditioned increases in self-administration in rhesus monkeys

Operant responding in three monkeys was maintained by intravenous presentations of morphine. Nalorphine produced reliable increases in morphine-reinforced responding. With successive daily nalorphine injections there was a decreased latency of self-administration responding for morphine, and substituted saline injections produced conditioned increases in morphine-reinforced responding.     

Behavioral method for study of pain in the monkey

A behavioral method is described in which increasing intensities of electric shocks were applied to the gasserian ganglia of alert monkeys. The animals were trained to press a lever to regulate the shock level. "Pain thresholds" were thereby obtained, and these thresholds were modified by varying the shock duration and by administration of morphine.     

不同给药时间间隔对吗啡诱导小鼠条件性位置偏爱模型的影响

为比较不同给药时间间隔下,同等剂量的吗啡诱导条件性位置偏爱(CPP)模型的差异,为后续抗吗啡依赖药物的筛选奠定基础,本研究建立了不同时间间隔的吗啡诱导CPP模型,(1)吗啡组(24 h):连续4 d皮下注射,上午注射吗啡(5 mg·kg?1),下午注射生理盐水,吗啡给药间隔24 h,建立CPP模型;(2)吗啡组(48 ...     

Tolerance to morphine-induced increases in [14C]catecholamine synthesis in mouse brain

Morphine sulfate increased the incorporation of carbon-14-labeled tyrosine into labeled catecholamines in the mouse brain. Tolerance was manifested by a shift to the right in the dose-response curve for morphine after mice were treated repeatedly with morphine. Naloxone, a specific morphine antagonist, also shifted the dose-response curve for morphine to the right.     

Paradoxical effects after microinjection of morphine in the periaqueductal gray matter in the rat

Paradoxical, concurrent hyper-and hyporeactivity of a profound nature to specific stimuli occurred when 10 micrograms of morphine was microinjected bilaterally into the periaqueductal gray matter of the rat brain. Both effects at this site were dose-dependent. The hyperreactivity (to previously neutral auditory and visual stimuli) was obtained only with intracerebrally injected morphine and never with intraperitoneally injected morphine or with other opiates administered either way. Rapid tolerance to toxic doses of morphine developed at this site, as well as cross tolerance of the hyporeactivity to painful stimuli between routes (intracerebral to intraperitoneal) of morphine administration. Both the hyper- and hyporeactivity were fully reversible by intracerebral injection of naloxone in the periaqueductal gray. Thus, the periaqueductal gray appears to be a major pathway for morphine action.     

Cellular adaptation to morphine in rats

The respiration of KCl-stimulated cortical slices of brain from control rats is markedly depressed by morphine, whereas the respiration of those from rats chronically dosed with morphine is unaffected. The results demonstrate an adaptation to morphine at the cellular level which is concomitant with the adaptation of the whole animal to morphine     

Cebus monkeys: effect on branching of gustavia trees

One 50-tree site with monkeys and one without were similar with respect to tree height and tree diameter, but the site with monkeys had trees with significantly more branches than those on the site without monkeys. Possibly removal of terminal buds during feeding by the monkeys releases the lateral buds from apical dominance and allows increased branching.     

Morphine tolerance, physical dependence, and synthesis of brain 5-hydroxytryptamine

Tolerance and physical dependence development to morphine in mice can be prevented by concomitant administration of cycloheximide. The fact that the rate of synthesis of brain 5-hydroxytryptamine (5HT) increases with tolerance to morphine suggests that the protein involved may be associated with 5HT synthesis. Inhibition of this synthesis with p-chlorophenylalanine markedly decreases tolerance and physical dependence development to morphine.     

Morphine: single-dose tolerance

Rats show a significant degree of tolerance to a second dose of morphine, with the degree of tolerance increasing the longer the delay between the two doses of morphine. To measure the morphine effect a foot-shock attenuation procedure that allowed the animal to adjust the shock intensity was used in studying delays of up to 180 days.     

Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson's disease

Lentiviral delivery of glial cell line-derived neurotrophic factor (lenti-GDNF) was tested for its trophic effects upon degenerating nigrostriatal neurons in nonhuman primate models of Parkinson's disease (PD). We injected lenti-GDNF into the striatum and substantia nigra of nonlesioned aged rhesus monkeys or young adult rhesus monkeys treated 1 week prior with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Extensive GDNF expression with anterograde and retrograde transport was seen in all animals. In aged monkeys, lenti-GDNF augmented dopaminergic function. In MPTP-treated monkeys, lenti-GDNF reversed functional deficits and completely prevented nigrostriatal degeneration. Additionally, lenti-GDNF injections to intact rhesus monkeys revealed long-term gene expression (8 months). In MPTP-treated monkeys, lenti-GDNF treatment reversed motor deficits in a hand-reach task. These data indicate that GDNF delivery using a lentiviral vector system can prevent nigrostriatal degeneration and induce regeneration in primate models of PD and might be a viable therapeutic strategy for PD patients.     

Biosynthesis of the morphine alkaloids

Tracer experiments, supported throughout by the analogous chemical transformations, have firmly established the biosynthetic sequence tyrosine -->norlaudanosoline --> reticuline --> salutaridine --> salutaridinol-I -->thebaine --> codeine --> morphine in Papaver somniferum. In general, the farther a precursor lies along this sequence, the more efficient its conversion to morphine in the intact plant. Several intermediates remain to be discovered, such as those lying between tyrosine and norlaudanosoline and between thebaine and codeine. Proof that morphine is made only by the reticuline-salutaridine route is still lacking and would require a careful comparison of the rate of morphine synthesis with the turnover rates for the various intermediates. More importantly, detailed knowledge of the mechanism of each biochemical step can come only with isolation of the enzyme system involved. The chemical oxidation of (-)-reticuline, to give salutaridine, can only be accomplished in very low (0.02 percent) yield (15, 26), whereas, even with whole plants, the biological incorporation of reticuline into the morphine alkaloids can reach 8 percent (13). One would like to know just how an enzyme system directs the oxidative cyclization of reticuline in the desired sense. Kleinschmidt and Mothes and Fairbairn and Wassel (27) have shown that the latex isolated from opium poppies is capable of transforming tyrosine into morphine. Perhaps further work with opium latex will provide the key to the remaining problems of morphine biosynthesis.     

Effect of deuteration of N--CH3 group on potency and enzymatic N-demethylation of morphine

Substitution of deuterium for the N-methyl hydrogens of morphine produced a significant reduction in the potency and lethality of morphine in mice regardless of the route of administration. There was no effect on the time of onset, maximal effect, or duration of action. N-demethylation by rat liver microsomal enzymes was characterized by a smaller reaction rate constant, a higher energy of activation, and a larger Michaelis constant with respect to the deuterated morphine. These findings indicated that deuteration of the N-methyl group of morphine not only caused reduction in potency, but also a reduction in the rate of oxidative N-demethylation, and a distinct weakening of the binding to the enzyme active centers.     

复方万年青胶囊联合美施康定治疗97例肺癌重度疼痛患者的临床观察

目的 观察复方万年青胶囊联合美施康定（硫酸吗啡缓释片）控制肺癌重度疼痛的效果。方法 回顾性调查97例肺癌重度疼痛患者,随机分为2组,对照组47例,采用美施康定治疗;试验组50例,采用复方万年青胶囊联合美施康定治疗,观察2组的抗癌痛效果、美施康定的人均维持日剂量、生活质量改善情况及不良反应发生情况。结果 与对照组相比,试验组抗癌痛效果较优（P<0.05）,美施康定的人均维持日剂量较小（P<0.05）,生活质量改善更明显（P<0.05）,毒副作用更小。结论 复方万年青胶囊联合美施康定治疗肺癌重度疼痛,能明显缓解癌痛,增强止痛效果,减轻不良反应,提高生活质量。     

Evidence for active immunity to morphine in mice

The serum from mice actively immunized with a morphine immunogen contained antibodies that could bind dihydromorphine. Morphine effects were diminished in these "immunized" mice, and the concentration of morphine in their plasma was altered.     

Urea cycle enzyme adaptation to dietary protein in primates

Activities of the five hepatic enzymes of the urea cycle increased two- to threefold in monkeys on a 60 percent protein diet compared with levels in monkeys on an isocaloric 6 percent protein diet. Equal adaptation occurred in rats on the same diets. These enzyme activities in adult humans approximate those of monkeys on a similar protein intake.     

Recovery of function after serial ablation of prefrontal cortex in the rhesus monkey

Rhesus monkeys with one-stage or serial ablation of sulcus principalis (prefrontal association cortex) were compared on three spatial tasks. On all tests, the serial monkeys made fewer errors than did the monkeys with onestage lesions. These results indicate that partial recovery of function can occur after extensive destruction of association cortex in the mature primate brain if the damage is distributed over a number of operations.     

Morphine-3-succinyl--bovine serum albumin: an immunogenic hapten-protein conjugate

Morphine-3-hemisuccinate was synthesized by reaction of morphine with succinic anhydride. This compound was conjugated to bovine serum albumin by the mixed anhydride method, and the degree of conjugation was determined by base hydrolysis of the conjugate, extraction, and measurement of free morphine. An average of 6.5 molecules of morphine were conjugated to each molecule of protein. Eleven rabbits immunized with varying doses of the conjugate were producing antibody 8 weeks later, as determined by a modification of the ammonium sulfate method, which measures primary binding of antigen by antibody.     

Behavioral effects in monkeys of racemates of two biologically active marijuana constituents

Both dl-Delta(8)- and dl-Delta(9)-tetrahydrocannabinol produced marked alterations of behavior in rhesus and squirrel monkeys. Squirrel monkeys appeared to have visual hallucinations. Continuous avoidance behavior of squirrel monkeys was stimulated by both drugs, but high doses of dl-Delta(9)-tetrahydrocannabinol also caused depression after the stimulant phase. Complex behavior involving memory and visual discrimination in rhesus monkeys was markedly disrupted by both drugs.