Typical and atypical antidepressant drug effects on locomotor activity after intra-accumbens injections in the rat.

Changes in spontaneous or drug-induced locomotor activity in rats were studied after injection of antidepressants in the nucleus accumbens. Antidepressant drugs, either alone or in combination with ergometrine, were injected bilaterally via fixed guide cannulas into the nucleus accumbens and locomotor activity was recorded during a period of 5 h. The after-effect, a long-lasting change in ergometrine-induced locomotor activity after priming with an antidepressant drug was also studied. It was concluded that: (a) The nucleus accumbens is a target site for antidepressant drugs in the rat. (b) Antidepressant drugs with mainly dopaminergic, noradrenergic or serotonergic features each show different effects in the test battery. (c) Typical as well as atypical antidepressants show common features.

Effect of metergoline, fenfluramine, and 8-OHDPAT on catalepsy induced by haloperidol or morphine.

The influences of the indirect serotonin agonist fenfluramine (5; 10 mg/kg s.c.), the serotonin antagonist metergoline (5; 10 mg/kg s.c.) and the 5-HT1A agonist 8-OHDPAT (0.1; 0.2; 0.46 mg/kg s.c.) on haloperidol-induced catalepsy in rats or mice and on morphine-induced catalepsy in rats were studied. Morphine-induced catalepsy was enhanced by fenfluramine and attenuated by metergoline, whereas neither fenfluramine nor metergoline had any effect on haloperidol-induced catalepsy. 8-OHDPAT strongly antagonised catalepsy induced by morphine or haloperidol. We conclude that serotonergic transmission plays a major role in effectuating morphine catalepsy but not in effectuating haloperidol catalepsy. The antagonistic effect of 8-OHDPAT suggests a secondary, modulating role for 5-HT1A receptor mediated events in both types of catalepsy.

(3,4-Dihydroxyphenylimino)-2-imidazoline (DPI) and its action at noradrenergic and dopaminergic receptors in the nucleus accumbens of rats: mesolimbic catecholamine receptors and hyperactivity.

Bilateral administration of ergometrine into the nucleus accumbens of rats pretreated 1-3 min earlier with intra-accumbens injections of noradrenaline, phenylephrine, clonidine and phentolamine has been found to produce a normal ergometrine-induced hyperactivity. In contrast, low doses of dopamine and (3,4-dihydroxyphenylimino)-2-imidazoline (DPI) and only high doses of clonidine and phentolamine have been found to attenuate the ergometrine response. These data together with the finding that phentolamine is unable to alter DPI's ability to suppress the ergometrine response provide direct evidence that the latter DPI effect is certainly not due to its ability to act as an agonist at alpha-NE receptors within the nucleus accumbens of rats.

The prognostic value of cortical magnetic stimulation in acute middle cerebral artery infarction compared to other parameters.

The prognostic value of magnetic evoked potentials (MEP), somatosensory evoked potentials (SSEP), age and radiological parameters was determined in 50 patients with acute middle cerebral artery infarction. We performed MEP and SSEP within 4 days and after 6 weeks and 3 months of the infarction and assessed clinical improvement by using the Barthel index (BI) and the Rankin scale. The localization and extent of the infarction was investigated by CT scanning or NMR. All parameters were correlated to clinical outcome and the prognostic significance of each parameter in addition to BI was determined. MEP, SSEP, and age were valuable prognostic parameters in predicting stroke outcome when used together with the BI. However, in stepwise regression analysis using all parameters simultaneously, only MEP and age significantly contributed to clinical outcome in addition to BI. Patients showed a better outcome when their MEP was normal or delayed, measured within 4 days of the infarction, compared to patients with absent MEP. Clinical outcome was better at a younger age.

A double-blind study of the efficacy of apomorphine and its assessment in 'off'-periods in Parkinson's disease.

Five patients with idiopathic Parkinson's disease with severe response fluctuations were selected for a randomized double-blind placebo-controlled study, concerning the clinical effects of subcutaneous apomorphine and its assessment in 'off'-periods. The study was designed as five n = 1 studies, in which every patient was his own control. The effect of apomorphine was studied by using the Columbia rating scale and quantitative assessments, using tapping, walking and pinboard. There was a significant positive effect of apomorphine, in a mean optimal dose of 2.7 mg, with a mean latency of onset of 7.3 min and a mean duration of response of 96 min. After pretreatment with domperidone, no significant adverse effects were observed. Tapping showed the highest correlation with rigidity and bradykinesia. Walking showed a high correlation with stability and gait. Pinboard testing did not give additional information. The first conclusion was that apomorphine proved to be a significantly effective dopamine agonist, proven now also by a double blind placebo-controlled study. Secondly it was concluded that assessment of clinical effect in parkinsonian patients can be performed best by combining the Columbia item tremor with tapping and walking scores.

Prodrug behaviour of nicotinoylmorphine esters.

Morphine and its nicotinoyl esters, dinicotinoylmorphine (nicomorphine), 6-mononicotinoylmorphine (6-MNM) and 3-mononicotinoylmorphine (3-MNM) were tested in mice for central activity to obtain time-effect profiles of these compounds in rats. Two effects, analgesia with the hot plate test and locomotor stimulation in activity cages were measured and nicomorphine, 6-MNM and 3-MNM were found to have a faster onset of action compared with morphine. The effects of 3-MNM and morphine lasted longer than the effect of nicomorphine and 6-MNM. The prodrug behaviour of 3-MNM and nicomorphine for morphine and 6-MNM, respectively, is discussed.

Distribution of motor unit potential velocities in short static and prolonged dynamic contractions at low forces: use of the within-subject's skewness and standard deviation variables.

Behaviour of motor unit potential (MUP) velocities in relation to (low) force and duration was investigated in biceps brachii muscle using a surface electrode array. Short static tests of 3.8 s (41 subjects) and prolonged dynamic tests (prolonged tests) of 4 min (30 subjects) were performed as position tasks, applying forces up to 20% of maximal voluntary contraction (MVC). Four variables, derived from the inter-peak latency technique, were used to describe changes in the surface electromyography signal: the mean muscle fibre conduction velocity (CV), the proportion between slow and fast MUPs expressed as the within-subject skewness of MUP velocities, the within-subject standard deviation of MUP velocities [SD-peak velocity (PV)], and the amount of MUPs per second (peak frequency=PF). In short static tests and the initial phase of prolonged tests, larger forces induced an increase of the CV and PF, accompanied with the shift of MUP velocities towards higher values, whereas the SD-PV did not change. During the first 1.5-2 min of the prolonged lower force levels tests (unloaded, and loaded 5 and 10% MVC) the CV and SD-PV slightly decreased and the MUP velocities shifted towards lower values; then the three variables stabilized. The PF values did not change in these tests. However, during the prolonged higher force (20% MVC) test, the CV decreased and MUP velocities shifted towards lower values without stabilization, while the SD-PV broadened and the PF decreased progressively. It is argued that these combined results reflect changes in both neural regulatory strategies and muscle membrane state.

Results of carpal tunnel release.

We evaluated, by means of a prospective study, the results of carpal tunnel release both clinically and electrophysiologically in 188 patients with a carpal tunnel syndrome. A questionnaire was completed by patient and surgeon pre- and post-operatively (6 and 12 months after operation), when physical examination, electromyography and nerve conduction tests were also performed. Full pre- and post-operative results were available for 136 patients and 82% of the patients were satisfied with the results of the operation. Symptoms caused by median nerve compression showed the greatest improvement and no fixed patterns with regard to unsatisfactory results were found. If pain persisted in the wrist, many patients considered the operation to have been unsuccessful. Electrophysiological improvement occurred in all patients and at 12 months follow-up, median nerve conduction was normal in 21% of cases. Thus distal sensory latency remained abnormal in 79% of the patients, emphasizing the need for caution when recurrence of carpal tunnel syndrome is diagnosed in such cases.