脑卒中患者恐惧疾病进展的研究现状

脑卒中患者在面对复杂的治疗期、漫长的康复期及难以预测的病情变化时容易产生对疾病或疾病进展的恐惧。恐惧疾病进展会损害脑卒中患者的身心健康和社会功能,最终影响患者的康复和预后。从恐惧疾病进展的定义、测量工具、国内外研究现状及影响因素几个方面进行综述,为临床护理人员深入了解脑卒中患者恐惧疾病进展现状、开展相关护理实践和临床研究提供依据。     

Spontaneous recovery of fear differs among early – late adolescent and adult male mice

Adolescence is a vulnerable period for developing anxiety-related mental disorders such as post-traumatic stress disorder (PTSD), which requires a long-term course of therapy when a traumatic event has been experienced during childhood. However, the biological mechanism underlying these age-dependent characteristics remains unclear. In the present study, we used early adolescent, late adolescent and adult (4-, 8-, and 15-week old) male mice to examine age differences in fear memory, fear extinction, and spontaneous recovery of fear. We also measured the activation of extracellular signal-regulated kinase (ERK) 2 in the dorsal hippocampus (dHip) and the basolateral amygdala (BLA) following a spontaneous recovery test. Our major findings were as follows: (1) early adolescent and adult mice did not recover the fear response; only late adolescent mice recovered the fear response. (2) The ERK2 in the dHip was more activated after the spontaneous recovery test in late adolescent mice than in adult mice, and the ERK2 in the BLA was more activated after the spontaneous recovery test in adult mice than in late adolescent mice. These results suggest that there exists a unique period in which spontaneous recovery occurs and that these late adolescent behavioral signatures may be related to alteration in the ERK2 phosphorylation in the dHip and BLA.     

Isolation impairs place preference conditioning to morphine but not aversive learning in mice

Morphine (8–100 mg/kg IP) induces place preference conditioning in mice. The effect of two different periods of isolation (15 and 30 days) was examined. Mice isolated for 15 days but not 30 days exhibited place preference conditioning to morphine (8 mg/kg). After 30 days of isolation morphine could not induce place preference conditioning with the following doses (8, 16, 64, 100 mg/kg). Social regrouping of male mice previously isolated for 30 days with naive female mice for 15 or 30 days resulted in a reappearance of the conditioned place preference to morphine (16 mg/kg). The specificity of this associative deficit was examined by testing learning in isolated compared to non-isolated mice in two distinct settings: escape learning in the Morris water maze and passive avoidance acquisition and retention. On the Morris water maze isolated mice did not differ from non-isolated mice regarding place learning, the probe trial or extinction. Isolated mice were unimpaired in passive avoidance acquisition and retention. It was concluded that the deficits in place preference conditioning were not the result of a global learning impairment in isolated mice. Received: 10 April 1996 /Final version: 20 September 1996     

Dental fear treatment: comparison of a video training procedure and clinical rehearsals

Abstract – Two types of fear desensitization, video training, and clinical rehearsals, were evaluated using psychometric tests, behavioral measures, and interviews for a group of 68 dental fear patients with high and low general trait anxiety. After treatment, a visual analogue scale (VAS) also tested the degree of perceived anxiety before going off to an unknown dentist. Results indicated no significant differences in dental fear reduction effects of the two types of desensitization. However, both treatments showed significant and meaningful effects when compared with a group of 75 dental fear patients on a waiting list who were also tested once at the beginning of the waiting period and again after 6 months. Only high general anxiety subjects resisted desensitization and failed standardized dental treatment tests. Exit interviews revealed that both groups named securing/accepting personnel, conversations about their fears and relaxation, in that order, as the most important factors in their dental fear reduction. Psychometric trust scores confirmed this. VAS scores showed a significant increase in fear level about the next dentist, also indicating trust as a major factor in reducing dental fear. Suggestions are made about which patient conditions can affect the choice of either of these training methods.     

Conditioned and unconditioned forelimb reflex systems in the cat: involvement of the intermediate cerebellum

 Temporary inactivation of the cerebellar interposed nuclei was used to assess the role of the intermediate cerebellum in the performance of forelimb cutaneo-muscular reflexes in the cat. The following types of reflexive responses were evaluated: the classically conditioned and unconditioned forelimb withdrawal responses and the forelimb tactile placing, hopping and magnet responses. The experiments tested the hypothesis that the intermediate cerebellum is involved in the performance of all the above forelimb reflexes. The forelimb withdrawal reflex was classically conditioned in a newly developed paradigm in which animals were first operantly conditioned to stand on four elevated platforms. Trained animals were microinjected with a γ-aminobutyric acid (GABA) agonist, muscimol, in the interposed nuclei, and the effects of inactivation of the intermediate cerebellar output on the forelimb reflexes were examined. The main findings of these experiments are that unilateral muscimol inactivation of the interposed nuclei in the cat abolished the expression of the classically conditioned limb flexion reflex, suppressed the performance of the unconditioned withdrawal reflex and, in parallel, downregulated the tactile placing, hopping and magnet postural responses in the ipsilateral forelimb. These observations are inconsistent with concepts indicating exclusive involvement of the intermediate cerebellum in the classically conditioned reflexes elicited by aversive stimuli. On the contrary, they support the hypothesis of a more global involvement of this structure in learned and unlearned defensive flexion reflexes and in automatic postural response systems. Received: 29 July 1996 / Accepted: 26 September 1996     

Reversal of stress-induced anhedonia by the dopamine receptor agonist,pramipexole

Chronic exposure to mild unpredictable stress has previously been found to depress the consumption of a palatable (1%) sucrose solution, and to attenuate food-induced place preference conditioning. In this study the effects of pramipexole (SND-919), a dopamine D₂ agonist, were studied during 7–9 weeks of chronic treatment. Pramipexole (1.0 mg/kg per day) reversed the suppression of sucrose intake in stressed animals, increasing sucrose intakes above the levels seen in untreated nonstressed controls. Pramipexole also increased sucrose intake in nonstressed animals; these effects were accompanied by increases in water intake and tended to correlate with weight loss. Drug-treated stressed animals also lost weight, but in this case water intake was unaffected. A second group of animals received a higher dose of pramipexole (2.0 mg/kg per day). The effects of the two doses were very similar. After three weeks of treatment, these animals were switched to a lower dose of pramipexole (0.1 mg/kg per day). Increases in sucrose intake were maintained over three weeks of treatment at the lower dose, with significant recovery of body weight. Two further groups received the same doses of pramipexole (1.0 mg/kg for 6 weeks or 2.0 mg/kg for 3 weeks followed by 0.1 mg/kg thereafter), but received intermittent (twice-weekly) drug treatment. Intermittent pramipexole treatments also tended to increase sucrose intakes, but the results were less consistent from week to week. Following 6–8 weeks of pramipexole treatment, food-induced place preference conditioning was studied in all animals. Untreated stressed animals showed no evidence of place conditioning. Normal conditioning was seen in both groups of stressed animals treated daily with pramipexole (at 1.0 and 0.1 mg/kg) and in the group treated twice weekly at the higher dose (1.0 mg/kg); intermittent treatment at the lower dose (0.1 mg/kg) was ineffective. The results indicate that pramipexole exerts rapid anti-anhedonic effects in the chronic mild stress model. This conclusion is complicated, but not undermined, by drug-induced weight loss and by the presence of significant drug effects in nonstressed control animals.     

Flavor preference conditioning by oral self-administration of ethanol

 Oral self-administration and operant tasks have been used successfully to confirm ethanol′s positive reinforcing effects in rats. However, in flavor conditioning tasks, ethanol is typically found to have aversive effects. The present studies explored this apparent paradox by examining the change in value of a flavor paired with orally self-administered ethanol in two different limited-access procedures. Rats were food-deprived and trained to drink (experiment 1) or to barpress for (experiment 2) 10% (v/v) ethanol during daily 30-min sessions using prandial initiation techniques. All rats were then exposed to a differential flavor conditioning procedure in which banana or almond extract was added to the drinking solution. One flavor (counterbalanced) was always mixed with ethanol (CS+), whereas the other flavor was mixed with water (CS–). By the end of conditioning, rats in both experiments drank more flavored ethanol than flavored water, confirming ethanol’s efficacy as a reinforcer. Moreover, barpress rates for CS+ exceeded those for CS– in the operant task. Ethanol doses self-administered in final sessions averaged about 1 g/kg. The effect of the flavor-ethanol contingency was assessed in preference tests that offered a choice between the two flavor solutions without ethanol. In both experiments, subjects developed a preference for the flavor that had been paired with ethanol. Thus, the outcome of flavor conditioning was consistent with that of the oral self-administration tasks in providing evidence of ethanol’s rewarding effects. These experiments confirm and extend previous studies showing that flavor aversion is not the inevitable result of flavor-ethanol association in rats. It seems likely that ethanol’s nutrient and pharmacological effects both contributed to the development of conditioned flavor preference. Received: 15 February 1997 / Final version: 11 June 1997