PubMed Health⌕ Search

Biomedical subjects

H Szechtman

Publications and source records attributed to H Szechtman.

At least 73 records · Page 4Linked to original sources
PubMed1990

Relation between motor asymmetry and direction of rotational behaviour under amphetamine and apomorphine in rats with unilateral degeneration of the nigrostriatal dopamine system.

The study examines whether in rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra, the direction of amphetamine- and apomorphine-induced rotations is determined by a bias to step more frequently with one hindleg. Results show that there is a strong asymmetry in usage of hindlegs under apomorphine but a weak one under amphetamine. Moreover, under apomorphine, virtually all steps are backward. Under amphetamine, however, steps are directed both backward and forward, although backward steps are relatively more prevalent when striatal dopamine depletion is nearly total. The different styles of rotation reflect the activation of pure turning under apomorphine, and turning combined with forward progression under amphetamine. It is suggested that presence of forward progression during turning depends on the capacity to modulate striatal activation. Moreover, the different styles of rotation are inconsistent with the hypothesis that a bias in leg usage sets the direction of turning. Instead, it seems that unilateral striatal activation sets the directionality of turning, independent of any hindlimb motor asymmetries.

Animals↗
PubMed1990

Dosing regimen differentiates sensitization of locomotion and mouthing to D2 agonist quinpirole.

The study examines whether the order of administering 2 doses of quinpirole (0.5 and 8 mg/kg) affects the development of behavioral sensitization, as measured by the amount of forward progression and mouthing. Results show that injection of the high dose greatly enhances the subsequent locomotor response to the low dose of quinpirole, but not vice versa. Mouthing activity is not influenced by order of administration but is significantly greater at the higher dose of quinpirole. The present findings are consistent with a hypothesis that locomotor sensitization involves down-regulation of a D1 tone normally inhibitory to D2 locomotor activation.

Animals↗
PubMed1990

Regional brain metabolism during auditory hallucinations in chronic schizophrenia.

Regions of the brain involved in language and attention were studied using [18F]-fluorodeoxy-glucose in PET. In nine chronic DSM-III schizophrenic patients who had persistent auditory hallucinations, ten who had recovered from hallucinations and ten normal controls. In none of the regions examined was metabolic activity significantly different in hallucinating patients compared with that in other groups. However, a pattern of seven significant correlations of metabolic activity between language regions and between frontal and parietal cortex characterised the hallucinating but not the other groups. Three of the seven correlations were significantly greater in hallucinating patients than in the two other groups, and six were greater in hallucinating patients than controls. Metabolism in Broca's region and its right-hemisphere homologue correlated positively and significantly in the hallucinating group, as it did in anterior cingulate and left superior temporal areas, and in right frontal and parietal areas. Hallucination ratings correlated with metabolism in the anterior cingulate region.

Adult↗
PubMed1989

D2-agonist quinpirole induces perseveration of routes and hyperactivity but no perseveration of movements.

The behavior in an open field of rats injected with the D2-agonist quinpirole (2 mg/kg; n = 10) and saline (n = 10) was analyzed in terms of routes and movements. Quinpirole induces perseveration of routes without inducing perseveration of movements. Perseveration of routes consists of repeated travel along a few paths in a limited portion of the environment. Lack of perseveration of movements was evidenced by the same distribution of lateral, vertical, and forward movements as in saline-treated animals. Quinpirole also increased the total amount of progression and the total number of movements performed by the rat's body parts along all dimensions of movements. Thus, under quinpirole, animals were hyperactive, stereotyped in route, but free in movement. This profile resembles behavior under low doses of amphetamine but not the behavior under either apomorphine or high doses of amphetamine. Thus, contrary to the current view, administration of a D2-receptor agonist is sufficient to produce a major component of dopamine-induced stereotyped behavior. It is suggested that quinpirole induces perseveration of route by affecting presynaptic release of dopamine, and that the organization of route is independent of the organization of movement.

Animals↗
PubMed1989

Biphasic effect of D-2 agonist quinpirole on locomotion and movements.

The effects of the D-2 agonist quinpirole on forward progression, and on vertical and lateral movements, were measured for 2 h in rats injected with either saline, 0.03, 0.125, 0.5 or 8 mg/kg of the drug. Results showed that the drug had a biphasic effect: the lowest dose decreased and the high doses increased the amount of locomotion and of movement. The decrease in activity produced by the low dose had its onset within minutes after administration of the drug; persistent and marked hyperactivity was observed from about 60-80 min after injection of 0.5-8 mg/kg of quinpirole. Moreover, in animals injected with intermediate doses, the excitation was preceded by a brief period of reduced locomotion. It is suggested that the biphasic effect may reflect two independent actions of the drug, possibly on activity in the nucleus accumbens.

Animals↗
PubMed1989

Increased frontal and reduced parietal glucose metabolism in acute untreated schizophrenia.

Frontal and parietal lobe metabolism was measured by [18F] fluorodeoxyglucose positron emission tomography in 8 never-medicated DSM-III schizophrenic patients and in 10 control subjects. Patients were in a psychotic episode at the time of this scan. Seven of eight had been ill less than 2 years and had only mild neurocognitive impairment. Frontal lobe glucose metabolism was significantly greater in schizophrenic patients than in controls. This finding differs from that of hypofrontality reported in chronic patients previously treated with neuroleptics. Relative glucose metabolism in the interior parietal lobe was significantly lower in schizophrenic patients than in controls. The frontal/parietal ratios were significantly greater in patients than in controls.

Acute Disease↗
PubMed1988

Effect of neuroleptics on altered cerebral glucose metabolism in schizophrenia.

This study examines whether the duration of treatment with antipsychotic drugs influences the regional distribution of cerebral [18F]2-fluoro-2-deoxy-D-glucose utilization as measured by positron emission tomography. Two groups of schizophrenic patients are compared with normal volunteers (n = 10). One group (n = 5) consisted of patients treated for one year, and the second (n = 12) of patients medicated for four to 14 years (mean +/- SD duration, 7.4 +/- 3.4 years). The first group was also examined before patients received their first dose ever of antipsychotic medication. One year of medication was not sufficient to alter the schizophrenic profile of cerebral cortical glucose activity but did elevate activity of the corpus striatum. Medication for 7.4 years also did not alter the schizophrenic pattern of frontal hyperactivity and posterior hypoactivity, although deviations from control values appeared less marked than after one year. On the other hand, in patients medicated for 7.4 years, there was perhaps an even greater increase in the activity of the corpus striatum and of the thalamus. Thus, duration of exposure to antipsychotic medication may affect the pattern of cerebral glucose activity; possibly, even longer exposure may contribute to the hypofrontality noted by others, although this can be confounded with the duration of illness as a factor. In considering the biological significance of the observed profile of cortical glucose activity, we introduce the concept of cerebral metabolic tone. We suggest that a disturbance of this tonus may account for some symptoms of schizophrenia and could be consistent with the hypothesis of abnormal developmental changes in the brains of schizophrenics.

Acute Disease↗
PubMed1988

Effect of the dopamine receptor agonist apomorphine on sensory input.

The study examines the hypothesis that changes in behavioural responsiveness induced by apomorphine reflect an effect of the drug on visual, tactile, vestibular, or proprioceptive sensory input. Rats were injected with apomorphine (1.25 mg/kg) and administered a neurological examination in which stimuli from the different sensory modalities were tested for their ability to elicit a limb placing response. Results indicate that these sensory stimuli were equally effective in eliciting reflex placing reactions in saline- and apomorphine-treated rats. Thus, contrary to the hypothesis, apomorphine does not appear to affect the reception of visual, tactile, vestibular, or proprioceptive sensory input. Tests of equilibration (righting) induced by static tilt revealed a fractionated response under apomorphine (0.6-5 mg/kg). Since the response to tilt probably involves striatal integration of vestibular and proprioceptive input, it is suggested that apomorphine disrupts sensory or sensorimotor integration.

Animals↗
PubMed1988

Sensitization and tolerance to apomorphine in men: yawning, growth hormone, nausea, and hyperthermia.

This study investigated whether the indices of dopaminergic function, yawning and growth hormone release induced by apomorphine, as well as the drug-induced nausea and hyperthermia, show sensitization or tolerance to repeated injections. Five normal volunteers received 12 injections of apomorphine hydrochloride (0.75 mg/70 kg) every 2 weeks. Yawning, as measured by the latency of onset and the time of peak activity, showed sensitization. The growth hormone response showed no change. Feelings of nausea and hyperthermia showed tolerance to repeated injections. These findings suggest that yawning may be a suitable index of dopaminergic function in studies of schizophrenia.

Adult↗
PubMed1988

Seasonal variations in prolactin levels in schizophrenia.

As part of an ongoing longitudinal study of drug-free schizophrenic patients, we serially sampled resting early morning prolactin levels in 10 subjects. In a preliminary analysis, these levels were compared to those found in matched normal control subjects over a 4-year period. Both control and schizophrenic subjects showed a marked annual variation in prolactin levels. Six schizophrenic patients sampled in each quarter of the year showed a significant annual rhythm, with prolactin highest in the spring (March-May). In seven schizophrenic patients and nine controls sampled at two seasons in the year, prolactin was significantly higher in spring-summer (March-August) than in fall-winter (September-February), with no difference between patients and control subjects.

Adult↗
PubMed1988

Longitudinal growth hormone studies in schizophrenia.

The growth hormone (GH) response to apomorphine hydrochloride (APO) was examined monthly in 12 schizophrenic patients on drug holiday for up to 22 months and compared with age- and sex-matched controls. There was more variability in the response of patients than controls on the first trial and on several subsequent challenges. Patients' and controls' GH responses to an APO challenge did not distinguish them from each other on the first trial. However, longitudinal data revealed that in a subgroup of five schizophrenic patients and five controls, studied for 12 consecutive trials, the GH response averaged over the 12 trials was significantly lower in the patients than in the controls. Moreover, when schizophrenics' responses on each successive trial were compared, responses decreased over time, but were significantly different from controls only in the later trials. Three of the patients were followed for more than 12 trials, and their GH responsivity increased in the later trials. GH response to APO was significantly correlated with positive symptom scores in three patients but not in four others. There was a trend toward an association between the occurrence of relapse and GH increment induced by APO. A significant association between change in body weight and change in GH response to APO was discovered, suggesting that a changing body weight may contribute to the variability in subjects' response to APO.

Adult↗
PubMed1988

Differences in the behavioral profile of circling under amphetamine and apomorphine in rats with unilateral lesions of the substantia nigra.

In rats with severe depletion of striatal dopamine, produced by a unilateral injection of 6-hydroxydopamine into the substantia nigra, amphetamine (2 mg/kg) induces circling towards the side of the lesion and apomorphine (0.25 mg/kg) induces circling in the opposite direction. In Experiment 1 we showed that under apomorphine, circling may be related to an asymmetry in stepping, but under amphetamine it is not. Specifically, under apomorphine, rats rotate almost exclusively by stepping (backwards) with the contralateral hindlimb while pivoting on the ipsilateral hindlimb. In contrast, under amphetamine, they rotate using a variety of stepping patterns, and there is no consistent asymmetry in using one hindleg for stepping and the other one for bearing weight. Considering the stepping patterns, it is suggested that rotations induced by apomorphine and amphetamine involve at least one and two variables, respectively (turning and turning plus forward progression). Furthermore, the results of Experiment 2 revealed that under apomorphine the direction of circling in a pool of water is reversed by edges, but under amphetamine it is not. In particular, under apomorphine, rats swim in the contraversive direction when in the middle of the pool but in the ipsiversive direction when swimming along the edge of the pool. In contrast, under amphetamine, they show little attraction for the edge and continue swimming in the ipsiversive direction, regardless of their position in the pool. It seems, therefore, that different behavioral mechanisms may underlie the rotations induced by apomorphine and amphetamine.

Amphetamines↗
PubMed1987

Electrophysiological correlates of stereotyped sniffing in rats injected with apomorphine.

Macroelectrodes were chronically implanted in the olfactory bulb, dorsal hippocampus, neocortex and under the mystacial pad in a group of rats. Recordings were taken during spontaneous behavior, during exploration of novel objects and odorous material, and during handling. Similar observations were made following injection of apomorphine (1.25-5 mg/kg, SC). The lower dose of apomorphine elicited a pattern of sniffing, olfactory bulb activity and vibrissal EMG which resembled closely the patterns observed in undrugged rats sniffing while in tactile contact with a novel object. However, unlike normal rats, the apomorphine-treated rats did not orient toward novel objects or odors. Apomorphine also elicited nearly continuous hippocampal rhythmical slow activity which occurred in correlation with head movements and locomotion. It is suggested that apomorphine elicits a motor pattern which resembles normal contact sniffing but which, unlike normal sniffing, is relatively impervious to control by visual and olfactory stimuli.

Animals↗
PubMed1986

Lateralized and compulsive exteroceptive orientation in rats treated with apomorphine.

A new behavioral test afforded the original demonstration of a compulsive and extremely lateralized taxis for edges in a minority (16%) of rats treated with the dopamine (DA) receptor agonist apomorphine (APO) (1.25 mg/kg, s.c.). APO also induced a reliable lateralization of locomotor direction in a rotometer in 29% of rats. The lateralizing effects of the drug on taxis for edges and rotational direction were not reliably associated, however, suggesting that these effects of APO are independent of each other. Interhemispheric asymmetries of DA receptors in functionally distinctive brain regions may underlie the diverse lateralizing effects of APO in subpopulations of rats.

Animals↗
PubMed1986

Behavior performed at onset of drug action and apomorphine stereotypy.

This study tests the hypothesis that stereotyped behavior induced by apomorphine reflects strengthening of behavior observed at the onset of drug action. Rats (n = 26) were injected with apomorphine (1.25 mg/kg) while being engaged in copulation. Contrary to the hypothesis, apomorphine did not strengthen ongoing copulation but arrested it. Instead of mating the males became engaged in behavior typically exhibited by rats injected with the drug. It is speculated that stereotyped behavior may be an expression of a drug-induced shift of attention or responsiveness to some particular range of stimuli.

Animals↗
PubMed1986

Postural asymmetry and lateralized rotation in normal rats administered apomorphine.

The study examines the hypothesis that the direction of circling exhibited by normal rats administered apomorphine reflects a drug-induced bias to use one specific hindleg for stepping and the other one for postural support. Results indicate that a majority of rats injected with this dopamine receptor agonist do show an asymmetry in the usage of the hindlegs (postural bias). However, the side of more frequent steppings does not predict the direction of circling. Moreover, postural bias may exist without lateralized circling. It is suggested that lateralized circling and postural asymmetry are two of several biases induced by apomorphine that may coexist in individual rats.

Animals↗
PubMed1986

Effects of pretreatment with naloxone on behaviours induced by a small dose of apomorphine.

The opiate antagonist, naloxone, was used to determine whether endogenous opioids modulate behavioural effects induced by a low dose of apomorphine. Before administering apomorphine (0.075 mg/kg) or saline, rats were pretreated with naloxone (1 mg/kg) or saline. Each subject received all 4 possible treatments (saline-saline, saline-apomorphine, naloxone-saline, and naloxone-apomorphine) in random order. Naloxone reduced the frequency and altered the timing of apomorphine-induced yawning, reduced the frequency of apomorphine-induced stretching, potentiated the effect of apomorphine on delaying grooming of the body, and did not affect the hypoactivity induced by apomorphine. Moreover, like apomorphine, naloxone itself reduced activity. Furthermore, naloxone and apomorphine injected together increased the latency to groom the face. These results suggest that in some circuits, endogenous opioids interact with dopaminergic autoregulatory mechanisms.

Animals↗