[Item response theory and its application in neurology. Measurement of activity limitations in neurologic patients]. / Item-response-Theorie und deren Anwendung in der Neurologie Messung von Aktivitätseinschränkungen neurologischer Patienten.

This article is concerned with the measurement of activity limitations in neurologic patients and with the application of the item response theory (IRT), especially the Rasch analysis, in analyzing activity ratings. Activity limitations of 166 patients with different neurologic disorders (e.g., stroke, traumatic brain injury) were assessed with the Functional Independence Measure (FIM) during their stay in a rehabilitation hospital. Data analysis was performed with the Rasch model, which allows testing the psychometric qualities of the FIM. Results indicate that the FIM has good psychometric qualities. However, results also show that the 18 FIM items define two statistically and clinically different indicators. Thirteen items define disability in motor functions. Five items define disability in cognitive functions. Separate analyses of the two scales help to improve the psychometric quality of the FIM.

Differential sensitivity of the caudal and rostral nucleus accumbens to the rewarding effects of a H1-histaminergic receptor blocker as measured with place-preference and self-stimulation behavior.

A recent series of studies in rats has demonstrated positively reinforcing and memory enhancing effects following lesions of the nucleus tuberomammillaris, which is the only known source of neuronal histamine. The aim of the present experiments was to assess whether inhibition of histaminergic neurotransmission in the ventral striatum has positively reinforcing effects. In Experiment 1 rats with chronically-implanted cannulae were injected with the H1 receptor blocker d-( + )-chlorpheniramine at doses of 0.1, 1.0 and 10.0 microg into the rostral or caudal parts of the nucleus accumbens, a brain region known to be involved in reward-related processes. Immediately after the treatment the animals were placed into one of four restricted quadrants of a circular open field (closed corral) for a single conditioning trial. During the drug-free test for conditioned place preference, when a choice among the four quadrants was provided, those rats injected with 10.0 microg chlorpheniramine in the caudal nucleus accumbens spent more time in the treatment corral, indicative of a positively rewarding drug action. In Experiment 2 the question was posed whether injection of chlorpheniramine into the nucleus accumbens influences electrical self-stimulation of the lateral hypothalamus. For this purpose rats were chronically implanted with two bipolar electrodes aimed at the lateral-hypothalami and with two additional guide cannulae aimed either at the rostral or caudal nucleus accumbens. After having established reliable self-stimulation behavior at one of the two electrode sites the animals were allowed to self-stimulate for one hour (baseline). Then they were unilaterally injected with 10.0 microg chlorpheniramine or vehicle and allowed to self-stimulate for another hour (test). On the next day the same procedure took place, except for the difference that the animals received an injection aimed at the hemisphere not treated so far. Animals treated with chlorpheniramine in the caudal and in the rostral nucleus accumbens displayed higher rates of ipsihemispheric self-stimulation behavior. Moreover, the animals treated with the H1 receptor blocker in the caudal nucleus accumbens displayed higher rates of ipsihemispheric self-stimulation than those having received an injection in the rostral pole. Upon completion of this part of the experiment all animals received an additional intraperitoneal treatment with chlorpheniramine (20 mg/kg) or vehicle, respectively, and were tested in the same way described above. This treatment also resulted in an amplification of intracranial self-stimulation behavior. These results support the hypothesis that histaminergic neurotransmission is involved in the inhibitory control of a central system subserving reward-related processes. The present data also further highlight the nucleus accumbens as functionally heterogenous along its rostrocaudal axis, with the caudal-shell subregion being more sensitive to antihistaminic induced reward than the rostral entity.

Enhanced learning by posttrial injection of H1-but not H2-histaminergic antagonists into the nucleus basalis magnocellularis region.

The aim of this study was to examine the effects of histaminergic antagonists on memory upon injection into the region of the nucleus basalis magnocellularis (NBM). In experiment 1, rats with chronically implanted cannulae were trained on the uphill avoidance task, which involves a punishment of a high-probability turning response on a tilted platform (negative geotaxis). Immediately after the training trial, that is, after a tail shock was administered upon performing the response, rats received one microinjection (0.5 microliter) of H1-receptor blocker chlorpheniramine (dose range 0.1 to 20 microgram) or the H2-receptor blocker ranitidine (same dose range) or saline into the NBM region. When tested 24 h later, rats treated with chlorpheniramine (20 micrograms) had significantly longer uphill latencies than vehicle controls and ranitidine-treated animals, indicative of superior learning of the avoidance response. In experiment 2, a test for possible proactive effects of posttrial chlorpheniramine on performance during the retention trial was performed. Animals were injected with either 20 micrograms chlorpheniramine or saline immediately after the training trial of the uphill task. One chlorpheniramine control group was treated with a delay of 5 h. Additional groups which received chlorpheniramine or vehicle after the training trial but no trail shock were included. When tested 24 h later, rats injected with 20 micrograms chlorpheniramine again exhibited significantly longer uphill latencies than did vehicle-injected rats. Retention latencies for the rats of the chlorpheniramine 5-h delayed group did not differ from those of the vehicle-injected rats, ruling out proactive effects of chlorpheniramine on performance. In summary, the histaminergic H1-blocker chlorpheniramine can enhance mnemonic functioning in addition to its reinforcing effects upon NBM injection as reported previously.

The H1- and H2-histamine blockers chlorpheniramine and ranitidine applied to the nucleus basalis magnocellularis region modulate anxiety and reinforcement related processes.

This study examined the effects of the H1-antagonist chlorpheniramine and the H2-antagonist ranitidine on reinforcement and anxiety-parameters following unilateral injection into the vicinity of the nucleus basalis magnocellularis (NBM). In Experiment 1, rats with chronically implanted cannulae were injected with chlorpheniramine or ranitidine (each at doses of 0.1, 1, 10 and 20 microg) and were placed into one of four restricted quadrants of a circular open field (closed corral) for a single conditioning trial. During the test for conditioned corral preference, when provided a choice between the four quadrants, only those rats injected with 10 or 20 microg chlorpheniramine spent more time in the treatment corral, indicative of a positively reinforcing action. None of the other doses of chlorpheniramine or of the H2-antagonist influenced rats' preference behavior. In Experiment 2, the elevated plus-maze (EPM) was used to gauge possible anxiolytic or anxiogenic effects of intra-basalis injection of chlorpheniramine or ranitidine (each at doses of 0.1, 1, 10 and 20 microg). A single injection of chlorpheniramine at 0.1 or 20 microg as well as ranitidine at 20 microg was found to exert anxiolytic-like effects in the EPM. Both compounds elevated the time spent on the open arms and increased scanning over the edge of an open arm. None of the other doses of the H1- and H2-antagonist influenced rats' behavior in the EPM. In sum, these findings show that H1- and H2-receptor antagonists differentially modulate reinforcement and fear-related processes in the NBM and thus, provide the first evidence for a behavioral relevance for the histaminergic innervation of this brain site.

Modulation of memory, reinforcement and anxiety parameters by intra-amygdala injection of cholecystokinin-fragments Boc-CCK-4 and CCK-8s.

This series of experiments examined the effects of the cholecystokinin (CCK) fragments Boc-CCK-4 and CCK-8s on memory, reinforcement and anxiety following unilateral injection into the central nucleus of the amygdala (CeA). In experiment 1, rats with chronically implanted cannulae were injected with CCK-8s or Boc-CCK-4 and were tested on a one-trial uphill avoidance task. Post-trial injection of 20 ng Boc-CCK-4 or 1 ng CCK-8s was found to improve the retention performance, whereas lower and higher doses had no effect. The hypermnestic effects of Boc-CCK-4 and CCK-8s were no longer evident when injection was performed 5 h, rather than immediately, after the learning trial. In experiment 2, the elevated plus-maze was used to gauge anxiogenous properties of intra-amygdala injections of Boc-CCK-4 and CCK-8s in memory-enhancing doses. The treatment with 20 ng Boc-CCK-4 and 1 ng CCK-8s did not influence the number of entries into and time spent on the open and enclosed arms of the maze as well as other anxiety-related behaviors. In experiment 3, possible reinforcing effects of the CCK-fragments were examined. After intra-amygdala injection of Boc-CCK-4 or CCK-8s in memory-enhancing doses the rats were placed into one of four restricted quadrants of a circular open field (closed corral) for a single conditioning trial. Subsequent tests for conditioned corral preference revealed no evidence for reinforcing or aversive effects of the CCK-fragments. In sum, these findings indicate that Boc-CCK-4 and CCK-8s facilitate memory processing upon injection into the CeA without exerting reinforcing or anxiogenous effects.

Lateralized attenuation of hypothalamic self-stimulation after injecting histamine synthesis blocker alpha-FMH into the E2 tuberomammillary subnucleus.

The tuberomammillary nucleus (TM), located in the posterior hypothalamic region, is the only known source of neuronal histamine. Unilateral lesions in the rostroventral part of this nucleus enhanced ipsihemispheric lateral hypothalamic self-stimulation behavior, suggesting that this region exerts inhibitory control over the neuronal systems related to reward or reinforcement processes. To examine whether the amplification of reinforcing stimulation following lesions of histamine synthesizing neurons is indeed histamine mediated, we blocked histamine synthesis unilaterally by injection of 200 microg alpha-fluoromethylhistidine into the E2 region of the TM, and assessed the effects on electrical self-stimulation behavior in the lateral hypothalamus (LH) of rats. Based on the finding that TM lesions facilitated such self-stimulation behavior, we hypothesized that this treatment would have similar effects. Unexpectedly, there was a sharp decrease in the rate of ipsihemispheric lateral hypothalamic self-stimulation following the injection of alpha-FMH compared to the contralateral hemisphere of treated animals as well as compared to the vehicle group. Response rates were most strikingly attenuated 1 h postinjection, but remained low over the whole 7 days of testing. Opposite behavioral effects of TM lesions and alpha-FMH application have been reported previously, and the effectiveness of alpha-FMH in reducing brain histamine levels is known to differ between brain regions. The fact that the alpha-FMH injection affected self-stimulation only in the ipsilateral hemisphere rules out an interpretation of the results in terms of unspecific effects of the treatment on arousal and other performance variables, and, instead, indicates a functional interaction with a subsystem linked to lateral hypothalamic reinforcement processes.

Comparison of neurokinin substance P with morphine in effects on food-reinforced operant behavior and feeding.

In the present study, substance P (SP) was injected intraperitoneally (IP), and its effects on operant behavior were assessed in rats, which had been trained to bar press for food reward on a fixed-ratio (FR) 20 schedule. These effects were compared with IP injection of morphine sulfate, which had previously been shown to strongly suppress operant responding on FR schedules. The IP injection of SP resulted in a dose-related decrement in response rates. SP in a dose range of 250-500 micrograms/kg decreased operant responding, whereas SP in a dose range of 5-50 micrograms/kg did not influence response rates. The IP injection of morphine (10 mg/kg) markedly suppressed operant responding. However, in contrast to the rate-decreasing effects of SP, this suppression was not selective for the reinforced lever as responding on the nonreinforced lever, used as a control, was also decreased. Furthermore, both injection of 10 mg/kg morphine and SP in a dose range of 250-500 micrograms/kg was found to reduce food intake when the animals had free access to food subsequent to the operant conditioning session. The present results provide the first evidence that systemically administered neurokinin SP can affect operant responding for food reward. The suppressive effects on operant behavior and feeding obtained with systemic SP or morphine are discussed with respect to recent findings showing that both drugs can modulate mesolimbic dopamine activity after systemic drug injection.