Biomedical subjects
Publications and source records attributed to G Colombo.
The present study demonstrates that the gamma-hydroxybutyric acid receptor antagonist, NCS-382, markedly reduces blood ethanol levels (BELs) in rats when ethanol is administered via the intragastric route, whereas it is completely ineffective when ethanol is injected IP. The reducing effect of NCS-382 on BELs is likely due to a lessened absorption of ethanol from the gastrointestinal tract.
BACKGROUND: The study aimed to assess the current and lifetime rates of post-traumatic stress disorder (PTSD) and major depression (MDD) among Nazi concentration camps survivors. METHODS: We investigated 51 Italian political deportees and 47 Resistance Movement veterans who reported traumatic experiences during active service. The Structured Clinical Interview for DSM-IV was used to assess the presence of PTSD and MDD. The Dissociative Experiences Scale and the shorter version of the Hopkins Symptoms Checklist were also administered. RESULTS: The lifetime rates of PTSD and MDD were 35.3% and 45.1% respectively among deportees and 4.3% and 6.4% among former partisans. The current rates for PTSD and MDD were 25.5% and 33.3% among deportees and 4.3% and 4.3% among former partisans. Dissociative symptoms were more severe among deportees than among Resistance movement veterans. CONCLUSIONS: Concentration camp internment, even for political reasons, appears to have severe long-term psychiatric consequences.
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Stimulation of motor activity induced by ethanol has been proposed to reflect the positive reinforcing properties of the drug. The present study was designed to assess whether voluntary ethanol intake would stimulate locomotor activity in Sardinian alcohol-preferring (sP) rats, selectively bred for high ethanol preference and consumption. Rats were habituated to a) consume either water alone (water-consuming rats) or ethanol (10%, v/v) as free choice together with water (ethanol-consuming rats) according to a 15-min limited access protocol for 10 consecutive days prior to the test, and b) explore an open field for 10 min immediately after the drinking session in a trial on 3 consecutive days before the test. On the test day, voluntary ethanol consumption in ethanol-consuming rats averaged 1.2 g/kg. Values for activity measures (time spent moving, number of square crossings and number of rearings) were significantly higher in ethanol- than in water-consuming rats at both 5- and 10-min intervals. These results suggest that the euphorigenic effects of ethanol, supposedly represented by the stimulation of locomotor activity, are part of the reinforcing properties of ethanol in sP rats.
The present study was designed to further investigate the pharmacological profile of the discriminative stimulus effects of gamma-hydroxybutyric acid (GHB). Drugs acting at the gamma-aminobutyric acid (GABA)B receptor (baclofen and CGP 35348), GABA(A)/benzodiazepine receptor complex (diazepam), N-methyl-D-aspartate (NMDA) receptor complex (dizocilpine), and cannabinoid receptor (WIN 55,212-2) were tested for substitution or blockade of the GHB interoceptive cue in rats trained to discriminate either 300 or 700 mg/kg of GHB i.g. from water in a T-maze, food-reinforced drug discrimination paradigm. Baclofen completely substituted for both training doses of GHB; however, its potency in substituting for GHB increased as the training dose of GHB was increased. CGP 35348 partially and completely blocked the cue elicited by 300 and 700 mg/kg of GHB, respectively. In contrast, diazepam partially substituted for 300 mg/kg of GHB, while failing to produce a GHB-appropriate response in the rat group trained to the higher GHB dose. Neither dizocilpine nor WIN 55,212-2 substituted for GHB. Collectively, these data suggest that: a) GHB produces a compound stimulus; and b) GABA(B)- and GABA(A)-mediated cues are prominent components of the mixed stimulus of GHB. However, the quality (i.e., the proportion of the component cues) of the stimulus varies as the training dose of GHB is increased; indeed, the contribution of the GABA(A)- and GABA(B)-mediated cues were smaller and greater, respectively, at 700 and 300 mg/kg of GHB training doses.
During human gait, cortical convergence on sural nerve reflex pathways was investigated by means of transcranial magnetic stimulation (TMS) of the cortex in five phases of the step cycle during human walking on a treadmill. Muscular responses to paired electrical and magnetic stimulation were compared with the linear summation of the individual stimuli. For both the tibialis anterior (TA) and biceps femoris (BF) muscles, the averaged data of four subjects showed a significant facilitation mainly in the swing phase of the step cycle. It is suggested that facilitation of corticospinal input onto cutaneous reflex pathways is enhanced specifically in these periods of the step cycle.
The effect of cannabinoid receptor activation and blockade on the propulsive activity in the mouse small intestine was assessed in the present study by measuring the transit of an orally administered, non-absorbable marker. The cannabinoid receptor agonist WIN 55,212-2 (R(+)-[2,3-dihydro-5-methyl-3[(morpholinyl)methyl]pyrrolo[1,2,3-de-1, 4benzoxazin-yl]-(1-naphthalenyl)methanone mesylate) inhibited, while the selective cannabinoid CB1 receptor antagonist SR 141716A (N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyraz ole-carboxamide) stimulated the marker transit. Furthermore, a per se non-effective dose of SR 141716A reversed WIN 55,212-2-induced reduction of the transit. The results of the present study suggest a role for cannabinoid CB1 receptors in the control of propulsive activity in the mouse small intestine.
The effect of ethanol withdrawal on hippocampal acetylcholine (ACh) release was investigated by brain microdialysis in rats rendered ethanol dependent by repeated forced administration of a 20% ethanol solution for 7 days. The behavioral signs of ethanol withdrawal were accompanied by an increase in hippocampal ACh output that was significantly 6 h after the last ethanol administration, reached a maximum (fourfold) at 12 h, and persisted for >72 h. Administration of diazepam (5 mg/kg, i.p.) or gamma-hydroxybutyrate (1 g/kg, intragastric) 12 h after the last ethanol administration completely antagonized, within 30 min, the increase in ACh output induced by ethanol withdrawal. Thus, the rapid and marked increase in ACh output might contribute to the changes in cognitive function associated with ethanol withdrawal, and the septohippocampal cholinergic system may play a major role in the response to withdrawal of addictive drugs.
The influence of body unloading (to 75, 50, and 25% body weight) on lower leg muscle activation during treadmill walking was investigated in patients with Parkinson's disease, age-matched and young healthy subjects. The aim of the study was to test the hypothesis that patients suffer from impaired extensor load receptor function. Although lower leg flexor muscle electromyographic (EMG) activity was relatively independent of body load, lower leg extensor EMG activity was markedly load sensitive. The EMG amplitude of the latter decreased with body unloading during stepping in all three groups of subjects. The load sensitivity progressively increased from patients to age-matched to young healthy subjects. In addition, the absolute level of leg extensor EMG amplitude during the stance phase of stepping became progressively larger from patients to age-matched subjects to young healthy subjects. It is suggested that decreased sensitivity of extensor load reflex mechanisms contributes to impaired gait in elderly subjects and is more pronounced in parkinsonian patients.
The effect of the cannabinoid CB1 receptor antagonist, SR 141716, on food intake and body weight was assessed in adult, non-obese Wistar rats. The daily administration of SR 141716 (2.5 and 10 mg/kg; i.p.) reduced dose-dependently both food intake and body weight. Tolerance to the anorectic effect developed within 5 days; in contrast, body weight in SR 141716-treated rats remained markedly below that of vehicle-treated rats throughout the entire treatment period (14 days). The results suggest that brain cannabinoid receptors are involved in the regulation of appetite and body weight.
Gamma-hydroxybutyric acid (GHB) and ethanol share several pharmacological similarities, suggesting that GHB may exert ethanol-like effects in the central nervous system. The present study was designed to test whether selectively bred ethanol-preferring rats would, unlike ethanol-nonpreferring ones, self-administer GHB, consistent with their higher preference for ethanol. Male ethanol-naive Sardinian alcohol-preferring (sP) and Sardinian alcohol-nonpreferring (sNP) rats were used. In Experiment 1, GHB solution (1% (w/v) in water) was initially offered as the sole fluid available for 14 consecutive days and then presented under the two-bottle, free-choice regimen, one bottle containing water and the other the GHB solution, for an additional 14 consecutive days. During the free-choice phase, high preference for GHB and intake of pharmacologically relevant daily doses of GHB developed in both rat lines, presumably because the 14-day no-choice period would unmask the reinforcing properties of GHB and lead to acquisition of GHB preference also in the supposedly less susceptible sNP rats. In Experiment 2, the forced GHB drinking phase was reduced to 3 days. Under the subsequent free-choice regimen, daily GHB preference and intake were initially low in both sP and sNP rats; however, after approximately 10 days, GHB preference and intake in sP rats rose progressively and then stabilized to significantly higher levels than in sNP rats throughout the entire free-choice phase. It is likely that episodic binges of GHB intake occurring during the first 10 days resulted in experiencing the reinforcing properties of GHB by sP but not sNP rats. The results of the present study suggest that a) sP rats are genetically more sensitive to the reinforcing effects of both ethanol and GHB than sNP rats; and b) disclosure of the higher sensitivity of sP rats to the reinforcing effects of GHB is a function of the length of the induction procedure. The results are also discussed in terms of differences in GHB receptors contributing to the predisposition to ethanol preference and avoidance, respectively.
Increasing evidence suggests that TKergic mechanisms might play a role in ethanol intake control. Preprotachykinin-A (PPT-A) mRNA brain levels were measured in Sardinian alcohol-preferring (sP) and Sardinian alcohol-nonpreferring (sNP) rats. PPT-A mRNAs were about 50% lower in sP than in sNP rats in the bed nucleus of the stria terminalis (BNST), whereas levels in the olfactory tubercle (Tu) were about 30% higher in sP than in sNP rats. Our findings suggest that altered PPT-A gene expression might contribute to the different ethanol preference and intake of sP opposite to sNP rats.
Recent studies have shown that a locomotor pattern can be induced and trained into paraplegic patients under conditions of body unloading using a moving treadmill. The present study investigated the behaviour of the locomotor pattern and also the relationship of its development to the spontaneous recovery of spinal cord function assessed by clinical and electrophysiological (tibial nerve somatosensory evoked potentials and motor evoked potentials) examinations. The earliest time that spinal locomotor activity could be induced was when signs of spinal shock had disappeared. This activity was distinct from spinal stretch reflex activity. In complete and incomplete paraplegic patients an increase of gastrocnemius electromyographic activity occurred during the stance phase of a step cycle with daily locomotor training over the whole training period of 12 weeks. This was coincident with a significant decrease in body unloading. In contrast to this, neither clinical nor electrophysiological examination scores improved after the onset of training in both patient groups. Only in incomplete paraplegic patients was there an insignificant increase in sensory and motor scores obtained in the neurological examination during the time period before onset of training. An improvement of locomotor function by training was also seen in patients with paraplegia due to a cauda lesion. Therefore, in patients with a spinal cord lesion training effects on muscles and tendons are present in addition to those on the spinal locomotor centres. The findings of this study may be relevant for future clinical treatment of paraplegic patients.
This study describes an amplitude independent assessment of changes in leg muscle EMG patterns in both complete and incomplete paraplegic patients during the course of locomotor training. The approach expresses the change as an approximation of the patients' gait EMG pattern compared with that of healthy subjects. The variation ratio (VR), coefficient of variation (CV) and Pearson's correlation coefficient (R), are used as measures of the dissimilarity/similarity of a set of wave forms. These parameters were evaluated for their ability to assess changes in the EMG pattern of the patients with respect to that of healthy subjects. The VR showed the best correlation to our data and was therefore considered to represent the optimum variable in the assessment of changes in EMG patterns.
The aim of this study was to evaluate the degree of contribution of supraspinal input to the generation of the compensatory leg muscle activation following stance perturbation. Therefore, evoked motor response (EMR) input-output relations of two different motor tasks were compared at 3 distinct periods: (1) the basic period of muscular activity during standing, i.e. when no additional cortical or spinal activity due to the different tasks is to be expected, (2) the pre-movement period with low background activity, when different spinal and cortical inputs to the motoneuronal pool can be assumed and (3) the period of plateau EMG activity of compensatory and voluntary motor task. Transcranial magnetic stimulation (TMS) just below the motor threshold was applied randomly at 19 different time-intervals before and during the onset of stance perturbation and for comparison during an equivalent voluntary foot-dorsiflexion task. Recordings of electromyographic (EMG) activity from the tibialis anterior (TA) and corresponding ankle-joint movements were made from both legs. Forward-directed displacements were induced by randomly-timed ramp impulses of constant acceleration upon a moveable platform. For comparison, leg muscle EMG was recorded during isometric foot dorsiflexion during stance while leaning back against a support. The stance perturbations were followed by a compensatory response (CR) in the TA with a mean onset time of 81 ms. During the basic period of muscular activity and the period of plateau EMG activity there was no significant difference of the input-output relation between stance perturbation and the voluntary motor task. However, in the voluntary task compared with the CR, there was significantly greater input-output relation (facilitation) of the EMR in the TA following TMS, which may be related to an increased cortical influence. In contrast to this result of the CR following stance perturbation, a facilitation of the EMR was described for hand muscles under corresponding conditions of automatic compensation for muscle stretch, suggesting a transcortical reflex loop. This difference in the results from upper and lower extremity muscles favors the assumption of a predominantly spinal generation of the TA-CR following stance perturbation.
Recent studies have shown that a locomotor pattern can be induced and utilized by paraplegic patients under conditions of body unloading using a moving treadmill. The present study investigated the behaviour of the locomotor pattern and also the relationship of its development to the spontaneous recovery of spinal cord function assessed by clinical and electrophysiological (tibial nerve somatosensory evoked potentials and motor evoked potentials) examinations. The earliest time that spinal locomotor activity could be induced was when signs of spinal shock had disappeared. This activity was distinct from spinal stretch reflex activity. In complete paraplegic patients the locomotor pattern improved spontaneously without training. This was coincident with both an increase of gastrocnemius electromyographic activity during the stance phase of gait and a decrease of body unloading. These effects reached a plateau after about 5 weeks. In complete and incomplete paraplegic patients a near linear increase of gastrocnemius electromyographic activity occurred during the stance phase of a step cycle with daily locomotor training over the whole training period of 12 weeks. This was also coincident with a significant decrease of body unloading. In contrast to this, neither clinical nor electrophysiological examination scores improved after the onset of training in both patient groups. Only in incomplete paraplegic patients was there recovery, albeit statistically insignificant, of spinal cord function according to the sensory and motor scores obtained in the neurological examination during the time period before onset of training. An improvement of locomotor function by training was also seen in patients with paraplegia due to a cauda lesion. Such training effects on muscles and tendons could be separated from those on the spinal locomotor centres. The findings of this study may be relevant for the future clinical treatment of paraplegic patients.
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