Histamine and spontaneous motor activity: biphasic changes, receptors involved and participation of the striatal dopamine system

The time- and dose-related effects of exogenous histamine on spontaneous motor activity and receptors involved were evaluated in male rats. Intracerebroventricular administration of histamine (5.4 and 54.3 nmol) produced a biphasic effect with initial transitory hypoactivity and later hyperactivity expressed by locomotion frequency in an open-field. The rearing frequencies were only reduced by all doses of histamine used. The histamine-induced hypoactivity was inhibited by the H3-antagonist thioperamide and was also induced by the H3-agonist N-alpha-methylhistamine. The histamine-induced hyperactivity phase was blocked by the H1-antagonist mepyramine. The H2-antagonist ranitidine increased locomotion and rearing frequencies. The participation of other neurotransmitters in the persistent hypokinetic effect induced by 135.8 nmol of histamine was determined by HPLC in the striatum and hypothalamus as counter-proof. A decreased DOPAC/DA ratio was observed only in the striatum. In the hypothalamus, low levels of 5HT were detected, probably not correlated with motor activity. In conclusion, the present results suggest that the exogenous histamine-induced hypoactivity response is probably due to activation of H3-receptors as heteroreceptors reducing the activity of the striatal dopaminergic system. This effect can partially overlap with the expression of the hyperactivity induced by H1-receptor activation. The participation of H2-receptors requires further investigation.     

Dissociating ventral and dorsal subicular dopamine D? receptor involvement in instrumental learning, spontaneous motor behavior, and motivation.

A series of experiments investigating the role of dopamine D? receptors in the ventral subiculum (vSUB) and dorsal subiculum (dSUB), 2 subregions of the hippocampal formation, found that D? receptor antagonism (3.0 nmol/0.5 μl SCH-23390 bilaterally) in the vSUB impaired instrumental learning and performance, reduced break point in progressive ratio (PR) tests, and produced an intrasession decline in responding during test sessions, but had no effect on spontaneous motor or food-directed behavior. In contrast, D? receptor blockade in the dSUB had no effect on instrumental learning, performance, PR break point, or food-directed behavior, but reduced spontaneous motor behavior. These results suggest a dissociation between the vSUB and dSUB with respect to the role of dopamine in various aspects of motivated and motor behavior. Further, D? activation in the vSUB may be a critical component of motivational arousal associated with learned contextual cues. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Regional differences in the effects of amphetamine withdrawal on dopamine dynamics in the striatum. Analysis of circadian patterns using automated on-line microdialysis

The purpose of the study is to determine the relationship between behavioral symptoms of amphetamine withdrawal and the extracellular concentration of dopamine (DA) in the dorsolateral caudate nucleus and the nucleus accumbens across the entire light-dark cycle. This was accomplished using automated on-line microdialysis sampling in behaving rats. Animals were pretreated with escalating doses of d-amphetamine (or saline) over a 6-week period and then were withdrawn from amphetamine for 3, 7, or 28 days before testing. There were regional differences in the effects of amphetamine withdrawal on the concentrations of DA and DA metabolites in dialysate. Early during withdrawal (3 and 7 days), when animals showed postamphetamine withdrawal behavioral depression (nocturnal hypoactivity), there was a significant decrease in DA and DA metabolites in the dorsolateral caudate nucleus and a disruption in the normal circadian pattern of DA activity. In contrast, there was no effect of amphetamine withdrawal on DA dynamics in the nucleus accumbens. By 28 days after the discontinuation of amphetamine pretreatment, after basal DA in the caudate returned to normal, there was a significant increase in basal DA metabolism in both the caudate and the accumbens. This increase in DA metabolism may be related to the expression of sensitization, including a hypersensitivity to an amphetamine challenge. It is concluded that the role of the dorsal striatum in psychostimulant drug withdrawal syndromes deserves further consideration.     

Behavioral depression during cocaine withdrawal is associated with decreased spontaneous activity of ventral tegmental area dopamine neurons.

Withdrawal from an escalating-dose, bingelike regimen of cocaine administration in rats produced significantly depressed levels of locomotor activity during the nocturnal portion of the day-night cycle. This effect was observed during the first 48 hrs of testing. Extracellular single-unit recordings of ventral tegmental area (VTA) dopamine (DA) neurons revealed no differences between saline- and cocaine-treated rats with respect to basal firing rates. However, significantly fewer spontaneously active VTA DA neurons were encountered in rats withdrawn from binge cocaine. As with the nocturnal hypoactivity, this effect was observed only during the first 48 hrs of withdrawal. These findings suggest that short-term DA neuron dysfunction during cocaine withdrawal temporally corresponds to behavioral disruptions that are similar to those described in human addicts. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Compensatory changes in striatal dopamine neurons following recovery from injury induced by 6-OHDA or methamphetamine: A review of evidence from microdialysis studies.

Reviews microdialysis experiments by E. Casta?eda et al (1989, in press), T. E. Robinson and I. Q. Whishaw (1987, 1988), and Robinson et al (1990) involving the association between recovery from dopamine (DA) depletion and normalization of extracellular DA. Data suggest that the 3 behavioral outcomes (sparing, recovery, and loss of function) associated with DA depletion may be related to differences in the ability of the residual population of DA neurons to maintain extracellular concentrations of DA; this effect may vary with lesion size. (French abstract) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Repeated isolation in the neonatal rat produces alterations in behavior and ventral striatal dopamine release in the juvenile after amphetamine challenge.

Rat pups were isolated from the mother and nest for 1 hr per day from Postnatal Day (PN) 2 to 9. At PN 27, rats were tested for behavioral responsiveness to 2.0 or 7.5 mg/kg amphetamine. Only isolated rats receiving the 7.5 mg/kg dose displayed increased activity scores, compared with nonisolated and nonhandled controls. Their increased activity is attributed to a slower latency to enter into stereotypy. In a second experiment, similarly treated groups were challenged by the 7.5 mg/kg dose during a session in which a microdialysis probe implanted in the ventral striatum was being perfused. The challenge drug elicited a much greater increase in dialysate dopamine in isolated vs nonisolated groups. Results are discussed with regard to dissociation between sensitized and subsensitized responses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Relationship between activity and hypothermia in immunosympathectomized mice.

Conduced 3 experiments in which 41 immunosympathectomized mice grew progressively colder relative to 41 controls at 3.5 and 22.5. C due to their reduced ability to vasoconstrict. Appropriate body temperature was maintained if these Ss were allowed to exercise in a running wheel. However, body temperature was not maintained in a stabilimeter-type situation, nor was activity heightened, suggesting that hypothermia is not a sufficient stimulus for activity. (17 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of dorsal and ventral vertical lobe electrolytic lesions on spatial learning and locomotor activity in Sepia officinalis.

This study aims to analyze the effects of electrolytic lesion, restricted to either the ventral or the dorsal parts of the vertical lobe (VL), on the behavior of cuttlefish (Sepia officinalis). Two behavioral tests were performed on sham-operated and lesioned cuttlefish: assessment of locomotor activity in an open field and determination of spatial learning abilities in a T maze. The results showed that ventral lesions of the VL led to marked impairment in the acquisition of spatial learning, whereas dorsal lesions of the VL increased locomotor activity in the open field and impaired long-term retention of spatial learning. This study establishes for the first time the existence of distinct functions in the ventral and the dorsal parts of the VL in cephalopods. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of hippocampal N-methyl-[D]-aspartate infusion on locomotor activity and prepulse inhibition: Differences between the dorsal and ventral hippocampus.

Prepulse inhibition (PPI) of the acoustic startle response and open-field locomotor activity were measured after bilateral infusion of N-methyl-[D]-aspartate into the ventral (0.10, 0.25, 0.50 Ag/side) and dorsal (0.10, 0.25, 0.50, 0.70 wg/side) hippocampus of Wistar rats. Dose-dependent hyperactivity and disruption of PPI-behavioral effects related to psychotic symptoms-were observed after ventral infusions but were virtually absent after dorsal infusions. This functional dorsal-ventral difference might be related to the different connections of the dorsal and ventral hippocampus with the amygdala, nucleus accumbens, and prefrontal cortex, which have been implicated in the regulation of locomotor activity and PPI. Hippocampal overactivity has been associated with schizophrenia. The findings suggest that overstimulation of the ventral hippocampal projections may contribute to behavioral outcomes related to psychotic symptoms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effects of dorsal versus ventral hippocampal, total hippocampal, and parietal cortex lesions on memory for allocentric distance in rats.

To test for the contribution of the parietal cortex and hippocampus to memory for allocentric spatial cues, the authors trained rats on a go/no-go task that required the rat to remember the distance between two visual cues. Total hippocampal lesions impaired working-memory representation for allocentric distance, whereas parietal cortex lesions resulted in only a transient impairment. In a second experiment, neither hippocampal nor parietal cortex lesions impaired allocentric distance discrimination. A third experiment showed that both the dorsal and ventral areas of the hippocampal formation must be destroyed to impair working memory for allocentric distance information. There appears to be a dissociation between the hippocampus and parietal cortex in mediating memory for allocentric distance information. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Relationship between changes in physical activity and plasma insulin during a 2.5-year follow-up study

The association between changes in physical activity, body weight, and diet and fasting plasma insulin was analyzed in a 2.5-year follow-up study of 146 men aged 50 to 60 years. Physical activity was assessed by a 7-day physical activity recall interview, diet by a 4-day food record, and plasma insulin radioimmunologically. Total physical activity decreased from (mean +/- SD) 45.1 +/- 10.1 to 39.0 +/- 6.1 metabolic equivalent (MET) hours (METh).d-1 and conditioning physical activity (> 5.0 METs) from 8.0 +/- 11.2 to 2.7 +/- 5.0 METh.d-1, whereas plasma insulin increased from 8.2 +/- 5.8 to 9.2 +/- 6.7 mU.L-1 and body weight from 80.5 +/- 12.0 to 81.6 +/- 11.6 kg during the follow-up period (P < or = .001 for all). The change in conditioning physical activity correlated inversely (r = -.34, P < .001) and change in body weight positively (r = .42,P < .001) with the change in plasma insulin level. With data adjusted for the baseline insulin level, cardiovascular health status, alcohol intake, change in body weight, smoking, age, and follow-up time, the odds ratio for an increase in fasting plasma insulin was 8.9 (95% CI, 2.1 to 37.1; P = .003) for men with the greatest decrease in conditioning physical activity (< -7 METh) compared with men who reported an increase in conditioning physical activity. The same logistic regression model showed an odds ratio of 9.9 (95% CI, 2.1 to 45.4; P = .003) for the increase in plasma insulin for subjects who gained more than 3.3 kg body weight compared with subjects who lost at least 0.6 kg. Men who consumed at least 12 g.d-1 alcohol at both examinations had an odds ratio of 12.8 (95% CI, 1.7 to 94.5; P = .012) compared with nondrinkers. These data suggest that in middle-aged men, a reduction in physical activity increases the risk for increased plasma insulin independently of alcohol intake and changes in body weight.     

A mechanistic account of striatal dopamine function in human cognition: Psychopharmacological studies with cabergoline and haloperidol.

The authors test a neurocomputational model of dopamine function in cognition by administering to healthy participants low doses of D? agents cabergoline and haloperidol. The model suggests that DA dynamically modulates the balance of Go and No-Go basal ganglia pathways during cognitive learning and performance. Cabergoline impaired, while haloperidol enhanced, Go learning from positive reinforcement, consistent with presynaptic drug effects. Cabergoline also caused an overall bias toward Go responding, consistent with postsynaptic action. These same effects extended to working memory and attentional domains, supporting the idea that the basal ganglia/dopamine system modulates the updating of prefrontal representations. Drug effects interacted with baseline working memory span in all tasks. Taken together, the results support a unified account of the role of dopamine in modulating cognitive processes that depend on the basal ganglia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Relationship between hippocampal theta activity and running speed in the rat.

The frequency of occurrence and amplitude of hippocampal theta waves induced by forced locomotion was proportional to speed of movement on a treadmill of 6 implanted male Sprague-Dawley rats. Although induction of hippocampal theta waves was related to the initiation of movement, it was not dependent upon proprioceptive feedback because it persisted in the resting S after a bout of running. It was possible to obtain cortical theta waves in the absence of hippocampal theta activity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Relationship between activity, rest, and free feeding in rats.

General activity and food intake were recorded concurrently in 9 albino free-feeding Wistar rats. Correlations of meal size with associated postmeal interval, activity, and rest were determined. Meal size was significantly positively correlated with both the length of the postmeal interval and the amount of rest in the postmeal interval, but not with the amount of activity in the postmeal interval. This suggests that the amount of energy expended following a meal is not related to the initiation of the subsequent meal and that some alternate mechanism underlies meal-to-meal regulation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of administering cocaine at the same versus varying times of day on circadian activity patterns and sensitization in rats.

The effects of different schedules of cocaine administration on circadian activity patterns and locomotor sensitization were studied. Rats received intraperitoneal injections of either saline or 20 mg/kg cocaine at either 24- or 33-hr intervals for 8 cycles (development). After a 2-day withdrawal, they were given a cocaine challenge in a novel environment. Rats given cocaine at 24-hr intervals were hypoactive 4 to 9 hr postinjection during development and, during cocaine challenge, showed sensitization of locomotor activity. Rats given cocaine at 33-hr intervals did not show these effects. On the 33-hr-period schedule, activity was enhanced beginning 24 hr after drug receipt. Different intermittent schedules of cocaine receipt may alter the vulnerability to cocaine, and altered vulnerability may be more likely when a subsequent cocaine injection interacts with a distal state of sensitivity produced by a prior injection. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Behavioral thermoregulation, core temperature, and motor activity: Simultaneous quantitative assessment in rats after dopamine and prostaglandin E1.

Determined the dose-response autonomic and behavioral thermoregulatory effects and the motor effects of dopamine (DA) and prostaglandin E1 (PGE1) injected into the lateral cerebral ventricles of male Sprague-Dawley rats. The present study was conducted with a computer-controlled thermocline that permitted freely moving Ss to select preferred ambient temperatures (7-39°C). All Ss were studied with the thermocline gradient both on and off to control for nonspecific effects. Results show that PGE1 (0, .1, .2, .5, 1.0 μg) produced a dose-related increase in core temperature and produced a dose-related selection of warmer ambient temperatures. DA (0, 50, 100, 200, 400 μg) produced a dose-related hypothermia and cold-seeking behavior. Without the gradient, DA-injected Ss did not become as hypothermic as in the gradient-on condition. When the gradient was available, Ss showed a significant rebound increase in core temperature 50-80 min after DA, which did not occur when the gradient was off. Overall, DA induced increases in motor activity, but, during the 1st 10 min after injection while the gradient was on, Ss made stable selections of cool ambient temperatures and showed reduced activity. Conversely, the behavioral effect of PGE1 did not facilitate the autonomically mediated heat gain. Findings emphasize the necessity of creating behavioral options for animals to fully evaluate drug effects on thermoregulation. (19 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Relationship between changes in somesthetic evoked responses and electroencephalographic findings in the child with hemiplegia

The results of somesthetic evoked response (SER) and electroencephalogram (EEG) records in 43 children with hemiplegic cerebral palsy have been compared. In all children there was a positive correlation between the SER changes and the affected side of the body. In 12 children the SER of the "damaged" hemisphere disappeared; in 31 children it was less than the response of the "healthy" hemisphere. On the other hand, a positive correlation between the EEG changes and the affected side was found in only 16 of the patients, and there was a dubious correlation in three cases. It is concluded that SER data are more accurate and reliable than EEG results. Moreover, SER findings allow cerebral damage to be suspected earlier than the EEG results and therefore are of greater prognostic value.     

Relationship between motoric and ideational activity preference and time perspective in neurotics and schizophrenics.

The dichotomous classification of motoric and ideational activity preference types was studied in relation to future and past time perspective in schizophrenic and neurotic groups. Special measures were constructed to classify Ss, to test the stability of the classification, and to measure future and past time perspective. The motoric-ideational activity preference classification was found to be reliable; ideational Ss had a greater extent of future time perspective than did motoric Ss; past time perspective was dependent upon the interaction of types and emotional disturbance grouping; motoric schizophrenics seemed to be more stimulus bound to the relative present; and ideational neurotics had a higher general-interest level than both the total motoric group and the total schizophrenic group. These results support the usefulness of the motoric-ideational classification as an organizing dimension of personality which shows both stability and construct validity. The results also revealed the potential value of studying the interaction of the motoric-ideational activity preference with types of emotional disturbance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

D? dopamine receptor mediation of social and nonsocial emotional reactivity in mice: Effects of housing and strain difference in motor activity.

The study examined the effects of isolation housing and the role of D? dopamine receptors on isolation-induced social and nonsocial (acoustic startle) reactivity in mice high (C57BL/6) and low (A) in motor activity. Isolation housing had no effect on acoustic startle but increased strain-specific forms of social reactivity. The D? agonist dihydrexidine (DHX) increased acoustic startle in isolated mice of both strains, but this effect was more pronounced in C57BL/6 mice. In this strain, DHX and the D? agonist SKF-81297 increased locomotor forms of social reactivity (e.g., escape, jump), whereas the D? antagonist SCH-23390 increased stationary reactivity (e.g., freezing). In A mice, DHX and SKF-81297 increased and decreased stationary reactivity, respectively, whereas SCH-23390 had no effect on these behaviors. Administration of SKF-81297 after pretreatment with SCH-23390 or the D? antagonist sulpiride confirmed the importance of D? receptors in mediating specific forms of social reactivity in C57BL/6 mice. These results suggest an important relationship between social reactivity and motor activity and an important, albeit strain-dependent, role for D? receptors in mediating specific emotional behaviors. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Relationship between serum angiotensin-converting enzyme activity and plasma plasminogen activator inhibitor activity in patients with recent myocardial infarction

BACKGROUND: An elevated level of angiotensin-converting enzyme (ACE) has been demonstrated to increase the risk of myocardial infarction. Plasminogen activator inhibitor (PAI) is the most important physiological inhibitor of tissue plasminogen activator in plasma. An elevated level of PAI has been reported to be associated with decreased fibrinolytic capacity and to constitute a marker of the risk for recurrent coronary thrombosis. METHODS: We measured the serum ACE activity and plasma PAI activity in 34 patients with recent myocardial infarction, and evaluated the correlation between these two values by linear regression analysis. We also administered captopril (37.5 mg/day) to 17 of these patients and placebo to the other 17 patients at random, and compared the changes in PAI activity and ACE activity in these two groups over a 1-month period. RESULTS: There was a significant correlation between the serum ACE activity and the plasma PAI activity at baseline in the patients (r = 0.498, P < 0.01). The captopril-treated patients showed significantly reduced PAI activity (P < 0.01), and a concomitant decrease in ACE activity. CONCLUSION: These results suggest that elevated ACE activity is associated with impaired fibrinolysis and that treatment with an ACE inhibitor improves the fibrinolytic function in patients with recent myocardial infarction. The results also suggest that the renin-angiotensin system plays a role in the increased risk of ischemic cardiovascular events when it is activated, and in the reduction of risk of recurrent myocardial infarction by ACE inhibition.