Taste preferences induced by trains of rewarding lateral hypothalamic stimulation of differing durations

The question of whether prolonged stimulation of the lateral hypothalamic area (LH) simply diminishes in rewarding effect or becomes aversive was tested in 32 rats using a taste preference technique. The animals were allowed to drink novel, coffee-flavoured water for 10 min, and then received 60 trains of LH stimulation with differing durations, at an intensity proven to be rewarding at 0.5 sec duration. In a test 24 hours later, those animals that had been stimulated with 1 or 5 sec trains showed a shift in preference from tap water to coffee water, but those stimulated with 10 sec trains did not. The results show that prolonged stimulation not only loses its positive reinforcement effect but becomes negative.     

Defensive reactions are counteracted by midazolam and muscimol and elicited by activation of glutamate receptors in the inferior colliculus of rats

 The inferior colliculus is involved in conveying auditory information of an aversive nature to higher cortical structures. Gradual increases in the electrical stimulation of this structure produce progressive aversive responses from vigilance, through freezing, until escape. Recently, we have shown that microinjections of NMDA into the inferior colliculus mimic these aversive effects and that the neural substrates responsible for learned escape behavior in the inferior colliculus are regulated by GABA−benzodiazepine mechanisms. In the present study, we extend these observations showing that unlearned aversive responses are also depressed by muscimol and midazolam, both GABA-benzodiazepine agonists, and that microinjection of glutamate, an excitatory amino acid, into the inferior colliculus can trigger freezing responses. Electrical stimulation of the inferior colliculus of rats placed inside an open field allowed the determination of thresholds for the aversive responses, alertness, freezing and escape. Systemic administration (3 and 5.6 mg/kg) as well as microinjections into the inferior colliculus of the anxiolytic compound midazolam (10, 20 and 40 nmol) caused increases in threshold for these aversive responses. Similar results were obtained following microinjections of the GABA-A agonist muscimol (0.1, 1 and 5 nmol) into this brainstem structure. Microinjections of low doses of glutamate (5 nmol), presumed to activate mainly AMPA/kainate receptors, into the ventrolateral division of the central nucleus of the inferior colliculus of rats placed inside a circular arena induced aversive reactions, characterized by freezing responses. However, higher doses of glutamate caused no apparent effects. GDEE, an AMPA/kainate receptor antagonist, inhibited, whereas AP7, a NMDA receptor antagonist, did not influence these responses. It is suggested that GABA-benzodiazepine processes modulate the expression of defensive reactions in the inferior colliculus and that activation of fast-acting excitatory amino acid receptors in this midbrain region can trigger the initial steps of the defense reaction without eliciting the motor explosive behavior usually seen following the activation of NMDA receptors. Received: 13 May 1998 / Final version: 12 August 1998     

呋喃唑酮厌恶疗法戒酒的临床观察及护理

目的：观察呋喃唑酮厌恶疗法戒酒的临床表现，探讨提高戒酒成功率的护理干预措施。方法：对23例酒依赖患者进行呋喃唑酮厌恶疗法，同时加强各阶段的护理干预。结果：一年随访戒酒成功率为87％。结论：患者有戒酒的愿望、家属的积极配合、全面的生活护理及适时的心理暗示是戒酒成功的重要条件。     

Multiplexed neurochemical signaling by neurons of the ventral tegmental area

The ventral tegmental area (VTA) is an evolutionarily conserved structure that has roles in reward-seeking, safety-seeking, learning, motivation, and neuropsychiatric disorders such as addiction and depression. The involvement of the VTA in these various behaviors and disorders is paralleled by its diverse signaling mechanisms. Here we review recent advances in our understanding of neuronal diversity in the VTA with a focus on cell phenotypes that participate in ‘multiplexed’ neurotransmission involving distinct signaling mechanisms. First, we describe the cellular diversity within the VTA, including neurons capable of transmitting dopamine, glutamate or GABA as well as neurons capable of multiplexing combinations of these neurotransmitters. Next, we describe the complex synaptic architecture used by VTA neurons in order to accommodate the transmission of multiple transmitters. We specifically cover recent findings showing that VTA multiplexed neurotransmission may be mediated by either the segregation of dopamine and glutamate into distinct microdomains within a single axon or by the integration of glutamate and GABA into a single axon terminal. In addition, we discuss our current understanding of the functional role that these multiplexed signaling pathways have in the lateral habenula and the nucleus accumbens. Finally, we consider the putative roles of VTA multiplexed neurotransmission in synaptic plasticity and discuss how changes in VTA multiplexed neurons may relate to various psychopathologies including drug addiction and depression.     

A comparison of neural responses to appetitive and aversive stimuli in humans and other mammals

Distinguishing potentially harmful or beneficial stimuli is necessary for the self-preservation and well-being of all organisms. This assessment requires the ongoing valuation of environmental stimuli. Despite much work on the processing of aversive- and appetitive-related brain signals, it is not clear to what degree these two processes interact across the brain. To help clarify this issue, this report used a cross-species comparative approach in humans (i.e. meta-analysis of imaging data) and other mammals (i.e. targeted review of functional neuroanatomy in rodents and non-human primates). Human meta-analysis results suggest network components that appear selective for appetitive (e.g. ventromedial prefrontal cortex, ventral tegmental area) or aversive (e.g. cingulate/supplementary motor cortex, periaqueductal grey) processing, or that reflect overlapping (e.g. anterior insula, amygdala) or asymmetrical, i.e. apparently lateralized, activity (e.g. orbitofrontal cortex, ventral striatum). However, a closer look at the known value-related mechanisms from the animal literature suggests that all of these macroanatomical regions are involved in the processing of both appetitive and aversive stimuli. Differential spatiotemporal network dynamics may help explain similarities and differences in appetitive- and aversion-related activity.     

Rodent models for compulsive alcohol intake

Continued seeking and drinking of alcohol despite adverse legal, health, economic, and societal consequences is a central hallmark of human alcohol use disorders. This compulsive drive for alcohol, defined by resistance to adverse and deleterious consequences, represents a major challenge when attempting to treat alcoholism clinically. Thus, there has long been interest in developing pre-clinical rodent models for the compulsive drug use that characterizes drug addiction. Here, we review recent studies that have attempted to model compulsive aspects of alcohol and cocaine intake in rodents, and consider technical and conceptual issues that need to be addressed when trying to recapitulate compulsive aspects of human addiction. Aversion-resistant alcohol intake has been examined by pairing intake or seeking with the bitter tastant quinine or with footshock, and exciting recent work has used these models to identify neuroadaptations in the amygdala, cortex, and striatal regions that promote compulsive intake. Thus, rodent models do seem to reflect important aspects of compulsive drives that sustain human addiction, and will likely provide critical insights into the molecular and circuit underpinnings of aversion-resistant intake as well as novel therapeutic interventions for compulsive aspects of addiction.     

Modulation of cocaine-induced place preferences by alcohol

Behavioral and physiological evidence suggests that alcohol modulates the effects produced by cocaine. To assess whether such modulation is evident with cocaine's affective properties, the present studies examined the effects of alcohol on cocaine-induced conditioned place preferences (CPP). In Experiment 1, male Sprague–Dawley rats were assigned to one of three groups based on whether they were conditioned with 20 mg/kg cocaine (Group C), 0.5 g/kg alcohol (Group A), or the combination (Group C/A). On the first conditioning trial, animals were injected with the drug(s) or vehicle and placed on one side of a place preference apparatus. On the next day, animals initially injected with drug received vehicle (and vice versa) and placed on the other side of the chamber. This cycle was repeated four times. Animals were then tested for their compartment preference. In Experiment 2, subjects were treated identically except that 1.5 g/kg alcohol was administered. In both experiments, Group C displayed a significant preference for the drug-paired compartment. Group A (in both experiments) showed no conditioned effect. In Experiment 1, Group C/A failed to display a significant preference, spending an amount of time in each compartment that was the numerical average of Groups C and A. In Experiment 2, the cocaine-induced preference was completely abated by 1.5 g/kg alcohol. These results indicate that alcohol produces a dose-dependent modulation of the affective properties of cocaine.     

护生“厌学”心理分析及相关对策

目的 探讨克服护生“厌学”心理的相关对策。方法分析护生“厌学”心理产生的原因，寻找相关对策。结果 发现护生“厌学”心理产生的原因有社会、学校、家庭及学生自身的因素。结论 通过只有减少社会不良因素干扰、改善学校教育环境，营造良好家庭教育环境，充分发挥学生的主体作用，才能帮助学生真正摆脱“厌学”的阴影。     

The contribution of gustatory nerve input to oral motor behavior and intake-based preference. I. Effects of chorda tympani or glossopharyngeal nerve section in the rat

Two-bottle intake tests and taste reactivity (TR) tests were used to reveal whether changes in ingestive behavior would follow bilateral section of either the chorda tympani (CT) or the glossopharyngeal (GP) nerve. Rats received two-bottle intake tests to compare 24-h ingestion of water to that of NaCl, MgCl2, quinine, or sucrose. Prior to each long-term intake test, rats received a 1 min, 1 ml intraoral infusion of the same chemical stimulus. Ingestive and aversive oral motor responses elicited by these 1 ml infusions were videotaped and subsequently analyzed. GP-section did not alter quinine or sucrose preference; overall, preference of MgCl2 and NaCl was also similar to controls. In contrast, TR tests in GP-sectioned rats revealed that most quinine, MgCl2 and NaCl stimuli elicited significantly fewer aversive oral motor responses. In addition, the latency of aversive responses to these 3 chemical stimuli was increased for these rats. Intake-based preference tests failed to show any difference between rats with CT nerve section and controls. In TR tests, however, CT-sectioned rats displayed significantly fewer ingestive oral motor responses to NaCl, MgCl2, and quinine than controls. Neither sucrose intake nor sucrose-elicited TR were altered by CT or GP nerve section. This report confirms the failure of long-term intake tests to uncover behavioral deficits following the section of gustatory nerves. In contrast, the use of a different behavioral test makes clear for the first time that gustatory nerve section has dramatic consequences on ingestive behavior. The examination of taste elicited oral motor behaviors reveals a coherent and nerve specific pattern of neurological deficit following peripheral nerve section.     

Central administration of nociceptin/orphanin FQ blocks the acquisition of conditioned place preference to morphine and cocaine, but not conditioned place aversion to naloxone in mice

Rationale Previous studies have suggested that nociceptin (known also as orphanin FQ) suppresses the rewarding potential of morphine and alcohol in the rat. However, little is known of the effect of nociceptin on the rewarding properties of these and other drugs in the mouse.Objective To determine the effect of nociceptin on opiate or psychostimulant-induced conditioned place preference, or naloxone-induced conditioned place aversion in mice.Methods C57BL6 mice were implanted with chronically indwelling intracranial cannulae targeted at the lateral cerebroventricle through which nociceptin (0.06, 0.6, or 6 nmol) could be administered. Animals were conditioned in an unbiased balanced paradigm to study the effect of nociceptin administration alone, or the effect of nociceptin on the acquisition of place conditioning to morphine, cocaine, or naloxone (all 7.6 mg/kg subcutaneous).Results Administration of 0.06 nmol nociceptin alone stimulated locomotion during conditioning sessions, but had no hedonic effects. In contrast, administration of 6 nmol nociceptin alone markedly reduced basal locomotion during the conditioning sessions and induced a mild place aversion. Both morphine and cocaine induced robust place preferences, the acquisition of which was dose dependently suppressed by administration of nociceptin at doses of 0.6 nmol and above. Conditioning with naloxone produced a robust place aversion that was only weakly blocked by the maximum dose of nociceptin tested.Conclusion Nociceptin blocks the rewarding properties of drugs in both narcotic analgesic and psychostimulant classes in the mouse. In contrast, nociceptin has only a minor effect on the negative affective state experienced following naloxone administration.