Social value framing of physical activity in European Member State policies: a content analysis.

Background: Engagement in physical activity (PA) benefits physical and mental health as well as many other areas of society. In Europe however, 1/3 adults do not meet minimum PA recommendations. Social value, and its quantification through social return on investment (SROI) evidence, may be a useful framing to enhance PA promotion. This study aimed to assess the current use of social value framing of PA in European Union (EU) policies. Methods: Content analysis of 45 EU member state policies which contain reference to PA was conducted to evaluate the presence of five social value domains and SROI evidence. Data was analysed using manual inductive coding, supported by DeepL translation and NVivo tools. Results: Social value framing was present to a certain extent in existing policies, with improved health being the most commonly referenced benefit of PA, followed by reference to social and community and then environmental benefits. Acknowledgement of the positive impacts of PA on wellbeing and education was the least present. Reference to SROI evidence was also limited. Generally, policies lacked holistic recognition of the social value of PA. Policies from the health sector were particularly limited in recognising the wider benefits of PA, whilst those from the environmental sector acknowledged the widest range of co-benefits. Conclusion: Adopting social value framing could be a useful approach for enhancing PA promotion. Whilst it is present to a certain extent in existing policy, this could be increased in terms of comprehensiveness to increase issue salience and multisectoral policy action.

Cerebrovascular responses to pathophysiological insult in diabetic rats.

Diabetes mellitus is associated with altered cerebrovascular responsiveness and this could contribute to the pathology of stroke in diabetic patients. In these studies, we used a model of haemorrhagic stroke (intrastriatal injection of 50 microl blood) to examine subacute perilesional perfusion and blood-brain barrier (BBB) integrity in spontaneously diabetic rats. Volumes of striatal oligaemia (blood flow < 35 ml 100 g(-1) min(-1)) were significantly increased (>300%) in diabetic rats with intrastriatal blood, compared to either non-diabetic rats with blood or control diabetic rats with striatal injection of silicon oil. However, the increase in BBB permeability was both qualitatively and quantitatively similar in diabetic and control rats. Poorer outcomes following haemorrhagic stroke in diabetic patients may thus result from dysfunctional cerebrovascular control, and particularly decreased dilatatory reserve.

Career advice--the role of appraisal.

The purpose of this article is to discuss the benefits of and to illustrate a framework for appraisal. The place of career advice in this process is mentioned, as is a brief discussion on assessment. From the point of view of the individual doctor, information to help him/her choose an appropriate career path should be readily available. It is more likely that a doctor will perform well throughout their career if in a career or occupation that suits them.

7-nitroindazole reduces cerebral blood flow following chronic nitric oxide synthase inhibition.

Blood flow and glucose utilization were measured in rat brain after chronic L-NAME treatment followed by acute 7-nitroindazole. Following chronic L-NAME, blood flow was not significantly different from control. Treatment with acute 7-nitroindazole reduced blood flow to the same extent in both chronic saline and L-NAME groups. Glucose utilization was unaffected. These results suggest that residual NOS activity in brain is sufficient to provide tonic, NO-dependent cerebrovascular dilator tone.

Effects of the specific serotonin reuptake inhibitor, citalopram, upon local cerebral blood flow and glucose utilisation in the rat.

The effects of the potent selective 5-HT reuptake blocking agent, citalopram (10 mg/kg, i.v.), on local cerebral blood flow (lCBF) and local cerebral metabolic rate of glucose (lCMRglu) were measured using [14C]iodoantipyrine (IAP) and [14C]2-deoxyglucose (2-DG) autoradiography, respectively. Significant decreases in lCBF were observed in nine of the 27 brain areas analysed, with significant decreases in lCMRglu observed in 17 areas. While decreases in blood flow were observed, it cannot be concluded that these were in fact the result of a direct action of 5-HT upon serotonergic receptors in cerebrovascular smooth muscle, since the dynamic relationship between flow and metabolism remains largely intact. The reductions in lCBF may be explained entirely by the secondary effects of depressed cerebral metabolic demand induced by citalopram which would, once again, question the role of specifically perivascular serotonergic nerve activity in the tonic control of cerebral blood flow.

Acute compartment syndrome of the thigh after joint replacement with anticoagulation.

We describe three patients with a compartment syndrome of the thigh, two after total hip replacement and one after total knee replacement. Two of the patients were fully anticoagulated. A compartment syndrome of the thigh is a rare, but important complication of joint replacement surgery if patients are receiving anticoagulants. Close observation is needed and when indicated monitoring of the intracompartmental pressure should be done. Early recognition of the signs and symptoms of an acute compartment syndrome and knowledge of the anatomy of the compartments of the thigh will help in the diagnosis and treatment of this potentially devastating complication.

Effects of nitric oxide modulation on tumour blood flow and microvascular permeability in C6 glioma.

C6 glioma strongly express nitric oxide synthase. Rats bearing C6 tumours were pre-treated with i.v. Ng-nitro-L-arginine methyl ester (L-NAME), 3-morpholinosydnonimine (SIN-1) or saline before local cerebral blood flow (LCBF) or tumour capillary permeability (TCP) was measured by the [14C]iodoantipyrine autoradiographic or [14C]alpha-amino-isobutyric acid techniques. L-NAME and SIN-1 caused significant TBF alterations (-44% and +136%, respectively) with less marked (-15% and +33%) alterations in normal brain. Calculated cerebrovascular resistance changes within tumour were indeed selective. Baseline TCP was increased compared with normal brain (20-fold). L-NAME and SIN-1 administration did not alter TCP. These effects have significant implications for human malignant glioma management. Selective i.v. manipulation of LCBF, without significant changes in TCP, could increase the efficacy of chemotherapy, radiotherapy or provide better peritumoural oedema control.

Intracerebral fetal raphé implants normalize hippocampal function but not cerebrovascular control in serotonin-depleted adult rat brain.

The effects of hypercapnia upon local cerebral blood flow and local cerebral glucose utilization were measured by quantitative autoradiography in parallel groups of rats (six per group) which 14-16 weeks previously had been treated with the serotonergic neurotoxin, methylenedioxymethamphetamine, followed by implantation of fetal raphé or basal forebrain tissues. Following the experiments, transplants were visualized by acetylcholinesterase histochemistry, and serotonergic reinnervation assessed using [3H]paroxetine binding to serotonin reuptake sites. In methylenedioxymethamphetamine-treated rats, contralateral to the implants, [3H]paroxetine binding was reduced by between 50 and 90% in the neocortex and hippocampus. Hippocampal glucose utilization was significantly increased in these rats, and the normal increase in flow which accompanies hypercapnia was also significantly enhanced. High levels of [3H]paroxetine binding were found within the raphé transplants (308 +/- 13 fmol/mg tissue). In host brain adjacent to the implant, binding levels were normalized, and in these same areas glucose utilization was also normalized. Basal forebrain implants had no effect upon either [3H]paroxetine binding or glucose utilization. Raphé transplants did not, however, alter the enhanced cerebrovascular response to hypercapnia induced by methylenedioxymethamphetamine, even in those areas where there was evidence of serotonergic reinnervation. The transplants also showed the same enhanced response. In conclusion, intracerebral fetal raphé implants normalize hippocampal function but not cerebrovascular control in serotonin-depleted adult rat brain, and despite not sharing the serotonergic deficit, blood flow in the implants follows that of the dysfunctional host.

Possible role for nitric oxide releasing nerves in the regulation of ocular blood flow in the rat.

AIM: To investigate the role of nitrergic nerves in the regulation of ocular blood flow. METHODS: Conscious, lightly restrained rats were treated with either the neuronal nitric oxide synthase inhibitor 7-nitroindazole (7-NI), or the nonselective inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), and ocular blood flow was measured ex vivo from tissue samples, using the fully quantitative [14C]-iodoantipyrine technique. RESULTS: In the peripheral circulation, L-NAME produced an increase in arterial blood pressure (+22%) while 7-NI had no effect. In contrast, both 7-NI and L-NAME produced significant decreases in ocular blood flow (-31% and -59% respectively). The ocular vascular resistance calculated from ocular blood flow and mean arterial blood pressure increased by 29% following 7-NI, but by 130% following L-NAME. CONCLUSIONS: Nitric oxide releasing neurons may play an important contributory role in regulating ocular blood flow.

Cerebrovascular effects of nitric oxide manipulation in spontaneously hypertensive rats.

1. Evidence that nitric oxide (NO) bioactivity is altered in chronic hypertension is conflicting, possibly as a result of heterogeneity in both the nature of the dysfunction and in the disease process itself. The brain is particularly vulnerable to the vascular complications of chronic hypertension, and the aim of this study was to assess whether differences in the cerebrovascular responsiveness to the NO synthase (NOS) inhibitors, NG-nitro-L-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI), and to the NO donor 3-morpholinosydnonimine (SIN-1) might indicate one possible source of these complications. 2. Conscious spontaneously hypertensive (SHR) and WKY rats, were treated with L-NAME (30 mg kg-1, i.v.), 7-NI (25 mg kg-1, i.p.), (0.54 or 1.8 mg kg-1 h-1, continuous i.v. infusion) or saline (i.v.), 20 min before the measurement of local cerebral blood flow (LCBF) by the fully quantitative [14C]-iodoantipyrine autoradiographic technique. 3. With the exception of mean arterial blood pressure (MABP), there were no significant differences in physiological parameters between SHR and WKY rats within any of the treatment groups, or between treatment groups. L-NAME treatment increased MABP by 27% in WKY and 18% in SHR groups, whilst 7-NI had no significant effect in either group. Following the lower dose of SIN-1 infusion, MABP was decreased to a similar extent in both groups (around -20%). There was no significant difference in MABP between groups following the higher dose of SIN-1, but this represented a decrease of -41% in SHR and -21% in WKY rats. 4. With the exception of one brain region (nucleus accumbens), there were no significant differences in basal LCBF between WKY and SHR. L-NAME produced similar decreases in LCBF in both groups, ranging between -10 and -40%. The effect of 7-NI upon LCBF was more pronounced in the SHR (ranging from -34 to -57%) compared with the WKY (ranging from -14 to -43%), and in seven out of the thirteen brain areas examined there were significant differences in LCBF. 5. Following the lower dose of SIN-1, in the WKY 8 out of the 13 brain areas examined showed significant increases in blood flow compared to the saline treated animals. In contrast, only 2 brain areas showed significant increases in flow in the SHR. In the rest of the brain areas examined the effects of SIN-1 upon LCBF were less marked than in the WKY. 6. Infusion of the higher dose of SIN-1 resulted in further significant increases in LCBF in the WKY group (ranging between +30% and +74% compared to saline-treated animals), but no significant effects upon LCBF were found in the SHR. As a result, there were significant differences in LCBF between SIN-1-treated WKY and SHR in six brain areas. In most brain areas examined, cerebral blood flow in SHR following the higher dose of SIN-1 was less than that measured with the lower dose of SIN-1. 7. Despite comparable reductions in MABP (approximately 20%) in both groups, calculated cerebrovascular resistance (CVR) confirmed that the vasodilator effects of the lower dose of SIN-1 were significantly more pronounced throughout the brain in the WKY (ranging between -3% and -50%; median = -38%) when compared to the SHR (ranging between -10% and -36%; median = -26%). In the animals treated with the higher dose of SIN-1, CVR changes were broadly similar in both groups (median = -45% in WKY and -42% in SHR), but with the reduction in MABP in SHR being twice that found in WKY, this is in keeping with an attenuated blood flow response to SIN-1 in the SHR. 8. The results of this study indicate that NO-dependent vasodilator capacity is reduced in the cerebrovasculature of SHR. In addition, the equal responsiveness to a non-specific NOS inhibitor but an enhanced effectiveness of a specific neuronal NO inhibitor upon LCBF in the SHR could be consistent with an upregulation of the neuronal NO system.

Effect of chronic inhibition of nitric oxide synthase on ocular blood flow and glucose metabolism in the rat.

AIMS: To investigate the effects of chronic administration of nitric oxide synthase inhibition on ocular blood flow and metabolic demand in the rat and to compare these effects with changes in the cerebral and peripheral circulation. METHODS: Male Sprague-Dawley rats were injected with the nitric oxide synthase inhibitor L-NAME (75 mg/kg i.p.), either on a single occasion only or once daily for 10 consecutive days. Controls were injected with saline. Regional blood flow and glucose metabolism were measured from tissue samples, using [14C]-iodoantipyrine and [14C]-2-deoxyglucose respectively, 1 hour after either acute L-NAME injection or 1 hour after the last injection of the chronic treatment protocol. RESULTS: Mean arterial pressure was significantly increased (+31%) following the acute injection (indicating peripheral vasoconstriction) and this effect was enhanced (+50%) following chronic treatment. In both the ocular and cerebral circulation, blood flow was decreased following acute treatment (-48% and -43% respectively). However, while this response was totally attenuated in the cerebral circulation following chronic L-NAME treatment (-4%), the ocular circulation remained responsive (-57%). Metabolic demand in brain and eye tissue, as reflected in the accumulation of 2-deoxyglucose, was unaffected by either acute or chronic treatment with L-NAME. CONCLUSION: Homeostatic mechanisms appear to be activated in the cerebral circulation which re-establish flow metabolism homeostasis, and the effect of L-NAME on cerebral blood flow is attenuated following repeated exposure. This process does not seem to happen in the ocular circulation and, thus, the ocular vasculature appears to behave more like those blood vessels which determine total peripheral resistance than the cerebral circulation. It remains to be seen whether the sustained decrease in blood flow in the eye is sufficient to compromise ocular function and render the eye susceptible to damage from chronic L-NAME induced oligaemia.

Comparison of the patterns of altered cerebral glucose utilisation produced by competitive and non-competitive NMDA receptor antagonists.

Recent studies indicate that competitive and non-competitive NMDA receptor antagonists can be readily distinguished by their effects on local cerebral glucose utilisation (1CGU). In the present study we compare the effects of the novel NMDA antagonist, (+)-1-methyl-1phenyl-1,2,3,4-tetrahydroisoquinoline (FR115427) on 1CGU, comparing its metabolic profile with that of the non-competitive NMDA receptor antagonist, dizocilpine (MK801) and of the competitive NMDA receptor antagonist CGS19755, using the 2-deoxyglucose metabolic mapping approach. Local cerebral glucose utilisation was measured in 80 anatomically discrete regions of the conscious rat brain using [14C]2-deoxyglucose quantitative autoradiography. Studies were initiated 10 min after the administration of FR115427 (0.1-3 mg/kg i.v.; n = 20), dizocilpine (0.03-0.3 mg/kg; n = 15), CGS19755 (1-30 mg/kg; n = 15) or saline (2 ml/kg; n = 5). Dizocilpine produced characteristic alterations in 1CGU with widespread increases in 1CGU in primary olfactory and limbic areas while reducing 1CGU in somatosensory and motor cortex. FR115427 produced a pattern of altered 1CGU which was broadly similar to that elicited by dizocilpine with increases in 1CGU in the pontine nuclei, presubiculum and hippocampus and reductions in somatosensory and motor cortex and within components of the auditory system. However, FR115427 was approximately 30-fold less potent than dizocilpine in this regard. In limbic structures, the effects of FR115427 were less pronounced than those produced by dizocilpine. Increases in 1CGU of 62-98% were found in retrosplenial, piriform and entorhinal cortex of dizocilpine-treated rats whereas these areas appeared relatively unaffected following FR115427 administration. A comparison of the pattern of metabolic response produced by each of these agents was performed by constructing a hierarchy of regional responsiveness using the f statistic: while focal differences in the metabolic profiles of dizocilpine and FR115427 were evident, a plot of the regional f values for dizocilpine and FR115427 revealed a strong overall relationship between the metabolic responses with a Pearson's product moment correlation of 0.78. In contrast, the correlation between the patterns produced by CGS19755 and that for dizocilpine or FR115427 was poor (r = 0.28 and 0.5 respectively).

Cerebrovascular responsiveness to NG-nitro-L-arginine methyl ester in spontaneously diabetic rats.

1. There is evidence that endothelial dysfunction is associated with diabetes mellitus. The purpose of the present study was to assess local cerebral blood flow (LCBF) and cerebrovascular responsiveness to the NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) in spontaneously diabetic insulin-dependent BioBred (BB) rats. 2. Diabetic rats, and non-diabetic controls, were treated with L-NAME (30 mg kg-1, i.v.) or saline, 20 min prior to the measurement of LCBF by the fully quantitative [14C]-iodoantipyrine autoradiographic technique. 3. There were no significant differences in physiological parameters (blood pH, PCO2, and PO2, rectal temperature, arterial blood pressure, or plasma glucose) between any of the groups of rats, and no difference in either the extent or the temporal characteristics of the hypertensive response to L-NAME between diabetic and non-diabetic rats. 4. In diabetic rats, a global reduction in basal LCBF was observed, although significant reductions (between -20 and -30%) were found in only 5 (mainly subcortical) out of the 13 brain regions measured. Following L-NAME injection, significant reductions in LCBF (between -20 and -40%) were found in the non-diabetic animals. In diabetic animals treated with L-NAME, a significant reduction in LCBF was measured only in the hypothalamus (-33%). 5. The cerebrovascular response to acute L-NAME is attenuated in spontaneously diabetic insulin-dependent BB rats. This would be consistent with the endothelial dysfunction in cerebral vessels, known to be associated with diabetes mellitus and it is possible that a loss of NO-induced dilator tone, amongst other factors, may underlie the observed reductions of basal LCBF in these animals.

Nitric oxide synthase is expressed in experimental malignant glioma and influences tumour blood flow.

The distribution and function of nitric oxide synthase (NOS) was studied in the rodent C6 implantation glioma model. Using a histochemical stain for NADPH diaphorase, which colocalises with NOS, morphological studies revealed non homogenous staining of the constituent tumour cells and the neoplastic endothelium. Immunocytochemical staining for macrophages (ED1, ED2) showed dense positivity at the tumour brain interface with more patchy positivity within the tumour mass. This finding suggests that both macrophages, which are known to produce large amounts of NO, and the C6 cells contribute to the NADPH diaphorase positivity. Administration of the NOS inhibitor Ng-nitro-L-argine methyl ester (L-NAME) significantly reduced both tumour (40%) and contralateral local cerebral blood flow (20%) compared to control animals. These findings demonstrate that (i) NOS is present in experimental malignant glioma; (ii) NO mediated mechanisms contribute to tumour blood vessel dilatation and blood flow regulation; and (iii) using this model there is a significant differential sensitivity of the tumour and brain parenchymal vascular beds to a NOS inhibitor. Further investigations are required to determine the potential therapeutic and biological relevance of these findings and the relative contributions of tumour cells, neoplastic endothelium and reactive macrophages to NO mechanism in gliomas.

Cerebrovascular consequences of repeated exposure to NG-nitro-L-arginine methyl ester.

1. Acute treatment with the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) produces cerebral oligaemia. The effects of repeated exposure to L-NAME upon cerebral blood flow were examined to determine whether the enhanced NOS inhibition reported following chronic treatment might reduce cerebral perfusion to ischaemic levels. 2. Rats were treated with L-NAME (75 mg kg-1, i.p.) once daily for 10 days. Local cerebral blood flow and glucose utilization were measured by [14C]-iodoantipyrine and [14C]-2-deoxyglucose quantitative autoradiography respectively, either 1 h or 15 h after the last injection. A second group of rats was injected (i.p.) only once with L-NAME, either 1 h or 15 h prior to the measurement procedures. 3. Mean arterial blood pressure (MABP) was significantly increased (+35%) 1 h after a single injection of L-NAME. Although the hypertension was reduced 15 h after the injection (+13%), MABP remained significantly higher than control. 4. Local cerebral blood flow was significantly decreased 1 h after a single injection of L-NAME (ranging from -45% to -54%), and remained so even after 15 h (-39% to -48%). At neither time-point was there any change in glucose utilization. 5. At 15 h after the final injection of the chronic L-NAME treatment protocol, MABP was significantly elevated from control (+58%) and was also significantly higher than at 1 h following a single injection (+20%). There was no effect upon the established hypertension when rats treated chronically with L-NAME were challenged with a further injection of the drug and MABP was measured 1 h later, suggesting saturation of NOS inhibition. 6. Although reduced, cerebral blood flow was not significantly different from control when measured 15 h after the last injection of the chronic L-NAME treatment. When rats treated chronically with L-NAME were subjected to a further challenge with the drug, cerebral blood flow was reduced when measured 1 h after the acute injection (ranging from -34% to -41%). There was however evidence of some attenuation in the response when compared to that measured 1 h after a single injection of L-NAME (ranging from -45% to -54%). Thus, the cerebral circulation shows no evidence of either sustained L-NAME-induced vasoconstriction or saturated NOS inhibition following 10 daily injections of L-NAME. Chronic L-NAME treatment had no effect upon cerebral glucose use. 7. The trend towards re-establishment of cerebrovascular dilator tone and the normalization of cerebral flow-metabolism relationships could explain the lack of any ischaemic damage found in chronically treated rats, but the loss of an extended autoregulatory range afforded by acute L-NAME treatment may be responsible for an increased incidence of stroke.

Inhibition of neuronal nitric oxide synthase by 7-nitroindazole: effects upon local cerebral blood flow and glucose use in the rat.

The novel nitric oxide synthase inhibitor 7-nitroindazole (7-NI) is relatively specific for the neuronal isoform of the enzyme and in this study we have used this compound to investigate the physiological role of perivascular nitric oxide-containing nerves in the cerebrovascular bed. Following injection of 7-NI (25 or 50 mg/kg, i.p.), cerebral blood flow and glucose utilization were measured in the conscious rat using the fully quantitative [14C]iodoantipyrine and 2-[14C]deoxyglucose techniques, respectively. Neither dose of the drug produced any change in arterial blood pressure, confirming a lack of effect upon the endothelial isoform of the enzyme, although there was a pronounced decrease in heart rate (-28% by 10 min postinjection). Throughout the brain 25 mg/kg 7-NI i.p. resulted in decreases in blood flow of between -20% in the hippocampus and -58% in the substantia nigra. Increasing the dose to 50 mg/kg resulted in a further generalized decrease, to almost -60% in parts of the thalamus and hippocampus, but in every animal this higher dose of 7-NI also produced randomly distributed areas of relative hyperaemia, which were most commonly found in those areas where the most intense hypoperfusion was otherwise in evidence. Despite these changes in blood flow, in all but a very few areas of the brain no significant decrease in glucose use was measured at either of the two doses of 7-NI. Thus despite the greater specificity of 7-NI for neuronal nitric oxide synthase, the cerebrovascular effects of the drug in vivo are very similar to that reported for the arginine analogues. However, these data do suggest that nitric oxide-releasing neurones in the brain may have an important role to play in the regulation of cerebral blood flow.

Enhanced cerebrovascular responsiveness to hypercapnia following depletion of central serotonergic terminals.

Serotonin-containing nerve fibres innervate cerebral blood vessels, but the source of this innervation and the physiological effects of perivascular serotonin release remain controversial. The purpose of the present study was to examine the effects of central serotonergic depletion upon the relationship between CBF and glucose utilization under both normo- and hypercapnic conditions. To induce the loss of serotonergic terminals, rats were injected twice daily for 4 consecutive days with 20 mg/kg of the specific serotonergic neurotoxin methylenedioxyamphetamine (MDA). Between 4 and 6 weeks later, local CBF and glucose utilization were measured using the fully quantitative [14C]iodoantipyrine and [14C]2-deoxyglucose autoradiographic techniques, respectively, and the efficacy of the lesioning protocol was assessed using [3H]paroxetine radioligand binding analysis. In all animals treated with MDA, there was a significant decrease in serotonin uptake sites throughout the brain, falling from 223 +/- 20 to 40 +/- 16 fmol/mg tissue in parietal cortex, for example, although the raphe nuclei themselves were unaffected (300 +/- 20 fmol/mg tissue in controls and 291 +/- 18 in MDA-treated rats). In normocapnic rats, the effects of MDA pretreatment upon blood flow and glucose use were slight and focally concentrated. However, when the animals were rendered hypercapnic, CBF was significantly higher in MDA-treated rats than in normal controls, for example, increasing from 356 +/- 22 ml 100 g-1 min-1 in frontal cortex of hypercapnic controls to 700 +/- 81 ml 100 g-1 min-1 in MDA-pretreated rats with similar levels of hypercapnia. In some brain areas of hypercapnic MDA-pretreated rats, blood flows were too high (> 800 ml 100 g-1 min-1) to be accurately quantified.(ABSTRACT TRUNCATED AT 250 WORDS)

Hyperaemia in rat neocortex produced by acute exposure to methylenedioxymethamphetamine.

Cerebral blood flow and glucose utilization were measured in rat neocortex, hippocampus and striatum following methylenedioxymethamphetamine injection (5 mg/kg, i.v.), using the tracers [14C]iodoantipyrine and [14C]2-deoxyglucose, respectively. In control rats, blood flow was coupled to glucose metabolism, but in methylenedioxymethamphetamine-treated rats, marked hyperperfusion was measured in frontal and parietal cortex with no change in glucose use. This suggests that methylenedioxymethamphetamine has the potential to disrupt cerebrovascular control.