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Orthostatic hypotension in patients, bed rest subjects, and astronauts.

Orthostatic hypotension after even short space flights has affected a significant number of astronauts. Given the need for astronauts to function at a high level of efficiency during and after their return from space, the application of pharmacologic and other treatments is strongly indicated. This report addresses the clinical problem of orthostatic hypotension and its treatments to ascertain whether pharmacologic or physiologic treatment may be useful in the prevention of orthostatic hypotension associated with space flight. Treatment of orthostatic hypotension in patients now includes increasing intravascular volume with high sodium intake and mineralocorticoids, or increasing vascular resistance through the use of drugs to stimulate alpha or block beta vascular receptors. Earlier treatment used oral sympathomimetic ephedrine hydrochloride alone or with "head-up" bed rest. Then long-acting adrenocortical steroid desoxycorticosterone preparations with high-salt diets were used to expand volume. Fludrocortisone was shown to prevent the orthostatic drop in blood pressure. The combination of the sympathomimetic amine hydroxyamphetamine and a monoamine oxidase inhibitor tranylcypromine has been used, as has indomethacin alone. Davies et al. used mineralocorticoids at low doses concomitantly with alpha-agonists to increase vasoconstrictor action. Schirger et al used tranylcypromine and methylphenidate with or without a Jobst elastic leotard garment or the alpha-adrenergic agonist midodrine (which stimulates both arterial and venous systems without direct central nervous system or cardiac effects). Vernikos et al established that the combination of fludrocortisone, dextroamphetamine, and atropine exhibited a beneficial effect on orthostatic hypotension induced by 7-day 6 degrees head-down bed rest (a model used to simulate the weightlessness of space flight). Thus, there are numerous drugs that, in combination with mechanical techniques, including lower body negative pressure to elevate transmural pressure, could be studied to treat orthostatic hypotension after space flight.

Animals↗

In vitro adsorption-desorption of phenethylamines and phenylimidazoles by a bentonite and a resin.

The adsorption of phenethylamines (dextroamphetamine, phentermine, mephentermine, diethylpropion), choline, and phenylimidazoles (levamisole and imazalil) was examined in vitro in aqueous solutions on bentonite and on lewatite at 25 degrees C. An ion-exchange mechanism prevails for lewatite and for bentonite up to 0.8 mEq X g-1. The organic cations are more strongly adsorbed on bentonite than on lewatite. On bentonite, the selectivity of adsorption follows the order: primary less than secondary less than tertiary phenethylamines. An interlamellar monolayer is formed. All drugs, except choline and imazalil, are adsorbed in excess of the cation exchange capacity of bentonite without observable Cl- adsorption and pH changes. Desorption is reversible for lewatite and partially irreversible for bentonite.

Adsorption↗

Effects of apomorphine and piribedil on pentylenetetrazol-induced seizures in mice.

Based on previous work examining the effects of dextroamphetamine on pentylenetetrazol (PTZ)-induced clonic seizure threshold, the objective of the present study was to determine the effects of two other dopamine agonists, apomorphine (AP) and piribedil, on PTZ seizures. TD50 and LD50 values for CD-1 mice were determined initially for the two drugs. Subsequently, dose- and time-response analyses established that AP decreased PTZ seizure threshold 15 min after administraton, but increased the threshold at 60 min. Piribedil elevated the seizure threshold, but like AP, did not exhibit a clear dose-response relationship. Subsequent blocker studies with phentolamine, (-)sotalol, pimozide, and atropine suggested the possible neurotransmitter systems involved in the modulation of the PTZ-induced seizures by AP and piribedil. Pimozide blocked the changes in seizure threshold induced by both drugs. Atropine also decreased the AP-induced increase in threshold at 60 min. The pattern of inhibition of seizure threshold changes induced by the neurotransmitter blockers suggested that piribedil blocked seizures by means of indirect actions on several neurotransmitters.

Animals↗

Acute autonomic nervous system effects of caffeine in prepubertal boys.

The effects of caffeine on autonomic activity were tested in 19 normal prepubertal boys. Subjects received placebo, 3 mg/kg, and 10 mg/kg caffeine in a random order (double blind) before three test sessions 48 h apart. Skin conductance (SC), heart rate (HR), and skin temperature (ST) were recorded during a rest period, a series of nonsignal tones, and a simple reaction time (RT) task. Caffeine increased the frequency of both spontaneous and elicited SC responses (SCR) under all conditions. Resting SC base level (SCL) was increased, and shorter SCR half recovery time also occurred in some periods. In contrast, caffeine decreased HR and motor activity at 3 mg/kg. Evidence of improved attention on caffeine was also obtained. The physiological effects are partially similar to the effects seen in clinical anxiety states, and they are also consistent with the physiological concomitants of good sustained attention. The profile of effects did not resemble those of dextroamphetamine in a similar population.

Attention↗

Canine cataplexy is preferentially controlled by adrenergic mechanisms: evidence using monoamine selective uptake inhibitors and release enhancers.

Narcolepsy is currently treated with anti-depressants to control REM-related symptoms such as cataplexy and with amphetamine-like stimulants for the management of sleepiness. Both stimulant and antidepressant drugs presynaptically enhance monoaminergic transmission but both classes of compounds lack pharmacological specificity. In order to determine which monoamine is selectively involved in the therapeutic effect of these compounds, we examined the effects of selective monoamine uptake inhibitors and release enhancers on cataplexy using a canine model of the human disorder. A total of 14 compounds acting on the adrenergic (desipramine, nisoxetine, nortriptyline, tomoxetine, viloxazine), serotoninergic (fenfluramine, fluoxetine, indalpine, paroxetine, zimelidine) and dopaminergic (amfonelic acid, amineptine, bupropion, GBR 12909) systems were tested. Some additional compounds interesting clinically but with less pharmacological selectivity, i.e., cocaine, dextroamphetamine, methylphenidate, nomifensine and pemoline, were also included in the study. All compounds affecting noradrenergic transmission completely suppressed canine cataplexy at low doses in all dogs tested, whereas compounds which predominantly modified serotoninergic and dopaminergic transmission were either inactive or partially active at high doses. Our results demonstrate the preferential involvement of adrenergic systems in the control of cataplexy and, presumably, REM sleep atonia. Our findings also demonstrate that canine narcolepsy is a useful tool in assessing the pharmacological specificity of antidepressant drugs.

Adrenergic Agents↗

Differential effects of amphetamine isomers on dopamine release in the rat striatum and nucleus accumbens core.

RATIONALE: Current medications for attention-deficit/hyperactivity disorder (ADHD) include some single isomer compounds [dextroamphetamine (D: -amphetamine, dexedrine) and dexmethylphenidate (Focalin)] and some racemic compounds [methylphenidate and mixed-salts amphetamine (Adderall)]. Adderall, which contains approximately 25% L: -amphetamine, has been successfully marketed as a first-line medication for ADHD. Although different clinical effects have been observed for D: -amphetamine, Adderall, and benzedrine; potential psychopharmacological differences on the level of neurotransmission between D: -amphetamine and L: -amphetamine have not been well characterized. OBJECTIVES: To evaluate potential differences in the isomers, we used the technique of high-speed chronoamperometry with Nafion-coated single carbon-fiber microelectrodes to measure amphetamine-induced release of dopamine (DA) in the striatum and nucleus accumbens core of anesthetized male Fischer 344 rats. Amphetamine solutions were locally applied by pressure ejection using micropipettes. RESULTS: The presence of L: -amphetamine in the D: ,L: -amphetamine solutions did not cause increased release of DA but did change DA release kinetics. The D: ,L: -amphetamine-evoked signals exhibited significantly faster rise times and shorter signal decay times. This difference was also observed in the nucleus accumbens core. When L: -amphetamine was locally applied, DA release was not significantly different in amplitude, and it exhibited the same rapid kinetics of D: ,L: -amphetamine. CONCLUSIONS: These data support the hypothesis that amphetamine isomers have different effects on release of DA from nerve endings. It is possible that L: -amphetamine may have unique actions on the DA transporter, which is required for the effects of amphetamine on DA release from nerve terminals.

Amphetamines↗

Processing efficiency of a verbal working memory system is modulated by amphetamine: an fMRI investigation.

RATIONALE: Working memory performance may be improved or decreased by amphetamine, depending on baseline working memory capacity and amphetamine dosage. This variable effect suggests an optimal range of monaminergic activity for working memory, either below or above which it is compromised. We directly tested this possibility with human participants by varying amphetamine dosage and measuring the efficiency of cortical processing in brain regions associated with working memory. OBJECTIVES: The modulation of cortical processing in a verbal working memory network by dextroamphetamine (D-amph) was examined using BOLD functional magnetic resonance imaging (fMRI) with healthy participants. The goal of the study was to test the hypothesis of an inverted U-shaped relationship between D-amph dose and processing efficiency of a verbal working memory system. METHODS: D-amph dosage was increased cumulatively every 2 h across four scanning sessions collected in a single day. The primary measure used for analyses in this study was the extent of activation in brain regions empirically defined as a working memory network. RESULTS: An inverted U-shaped relationship was observed between the amount of D-amph administered and working memory processing efficiency. This relationship was specific to brain areas functionally defined as working memory regions and to the encoding/maintenance phase (as opposed to the response phase) of the task. CONCLUSION: The results are consistent with the hypothesis that the neurochemical effects of amphetamine modulate the efficiency of a verbal working memory system. The effect of amphetamine on working memory in healthy individuals may provide insight regarding the working memory deficits seen in schizophrenia, given the overlap between neurochemical systems affected by amphetamine, and those disordered in schizophrenia.

Adult↗

Tourette's syndrome: are stimulants safe?

Clinicians commonly encounter children with comorbid attention deficit hyperactivity disorder (ADHD) and the tic disorder Tourette's syndrome. The pharmacologic treatment of children with this particular combination of conditions has been problematic because of long-standing warnings against using psychostimulants due to concerns about worsening tics. The basis for these warnings was anecdotal clinical observations. A recent group of placebo-controlled, double-blinded clinical trials have consistently shown that certain stimulants, particularly methylphenidate and dextroamphetamine, are effective, well tolerated, and safe when administered to treat ADHD in children with tics. Methylphenidate appears to be the best-tolerated stimulant compound, with tics often lessening during treatment.

Animals↗

Cognitive Impairment Following Traumatic Brain Injury.

Cognitive impairments due to traumatic brain injury (TBI) are substantial sources of morbidity for affected individuals, their family members, and society. Disturbances of attention, memory, and executive functioning are the most common neurocognitive consequences of TBI at all levels of severity. Disturbances of attention and memory are particularly problematic, as disruption of these relatively basic cognitive functions may cause or exacerbate additional disturbances in executive function, communication, and other relatively more complex cognitive functions. Because of the high rate of other physical, neurologic, and psychiatric syndromes following TBI, a thorough neuropsychiatric assessment of the patient is a prerequisite to the prescription of any treatment for impaired cognition. Psychostimulants and other dopaminergically active agents (eg, methylphenidate, dextroamphetamine, amantadine, levodopa/carbidopa, bromocriptine) may modestly improve arousal and speed of information processing, reduce distractibility, and improve some aspects of executive function. Cautious dosing (start-low and go-slow), frequent standardized assessment of effects and side effects, and monitoring for drug-drug interactions are recommended. Cognitive rehabilitation is useful for the treatment of memory impairments following TBI. Cognitive rehabilitation may also be useful for the treatment of impaired attention, interpersonal communication skills, and executive function following TBI. This form of treatment is most useful for patients with mild to moderate cognitive impairments, and may be particularly useful for those who are still relatively functionally independent and motivated to engage in and rehearse these strategies. Psychotherapy (eg, supportive, individual, cognitive-behavioral, group, and family) is an important component of treatment. For patients with medication- and rehabilitation-refractory cognitive impairments, psychotherapy may be needed to assist both patients and families with adjustment to permanent disability.

Journal Article↗

Countermeasures for sleep loss and deprivation.

Sleep deprivation is ubiquitous and carries profound consequences in terms of personal and public health and safety. There is no substitute for a good night's sleep. Sleep that is optimal in quality and quantity for individuals, factoring in their age and personal sleep requirements, will minimize sleep debt and maximize daytime performance. Therefore, setting aside an adequate amount of time for sleep should be a priority; sleep should not be sacrificed at the expense of other activities of daily living. Nevertheless, there are certain therapeutic countermeasures available for individuals who are unable to obtain adequate sleep because of medical or sleep-related conditions (eg, narcolepsy, obstructive sleep apnea) when excessive daytime sleepiness is the main feature of the condition, or residual sleepiness despite treatment for the main conditions is present. These therapeutic countermeasures may also be considered in situations in which occupational constraints (eg, rotating shift work, military duty) dictate that constant or heightened vigilance is important or critical to work performance, crucial decision making, and/or survival. Exploration of the causes of sleep loss or deprivation, whether it is voluntary, or work or family induced, and/or the effects of a medical or sleep disorder, is a necessary first step in the evaluation of a patient who has significant daytime fatigue or sleepiness. Wake-promoting substances and medications such as caffeine, modafinil, methylphenidate, and dextroamphetamine may be considered in situations in which sleep loss is unavoidable or persists despite treatment of an underlying disorder that is characterized by or associated with daytime fatigue or sleepiness.

Journal Article↗

The effect of methylphenidate on urinary catecholamine excretion in hyperactivity: a partial replication.

Children with attention deficit disorder with hyperactivity were treated with methylphenidate HCl (0.74 +/- 0.2 mg/kg/day) for 2 weeks in an open trial to assess changes in the urinary excretion of catecholamines and behavior. The purpose of this study was to confirm earlier work that methylphenidate has a distinctly different effect on urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) excretion as compared to earlier studies with dextroamphetamine. Results confirmed the earlier finding that methylphenidate does not significantly change urinary MHPG excretion. No significant relationship was found between behavioral change and any of the urinary catecholamines or metabolites measured.

3,4-Dihydroxyphenylacetic Acid↗

Persistent sensitization of dopamine neurotransmission in ventral striatum (nucleus accumbens) produced by prior experience with (+)-amphetamine: a microdialysis study in freely moving rats.

In humans the repeated use of amphetamine (AMPH) produces a hypersensitivity to the psychotogenic effects of AMPH that persists for months to years after the cessation of drug use. To explore the neurobiological basis of this phenomenon the long-term effects of dextroamphetamine [+)-AMPH) on brain monoamines and behavior were studied in an animal model of AMPH psychosis. An escalating dose pretreatment regimen (from 1 to 10 mg/kg over 5 weeks) was used to mimic the pattern of drug use associated with the development of addiction and AMPH psychosis. The effect of pretreatment with AMPH on dopamine (DA) release in the ventral striatum (nucleus accumbens) was determined by measuring the extracellular concentrations of DA and DA metabolites using in vivo microdialysis, both before and after an AMPH challenge. The postmortem tissue concentrations of DA, serotonin and their metabolites were measured to determine if this treatment was neurotoxic. Escalating doses of (+)-AMPH were not neurotoxic, and 25-30 days after the cessation of drug treatment animals showed relatively normal levels of spontaneous motor activity across the day-night cycle. However, AMPH pretreatment produced robust behavioral sensitization. Animals showed a marked hypersensitivity to the motor stimulant effects of an AMPH challenge, even after 15-20 days of withdrawal. Most importantly, this hyperdopaminergic behavioral syndrome was accompanied by significantly elevated DA release in the ventral striatum. In contrast, AMPH pretreatment had no effect on the basal extracellular concentrations of DA.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

Effects of several partial dopamine D2 receptor agonists in Cebus apella monkeys previously treated with haloperidol.

Eight Cebus apella monkeys were treated with haloperidol for 2 years. Five monkeys had developed mild oral tardive dyskinesia and all were primed for neuroleptic induced dystonia, thus serving as a model for both chronic and acute extrapyramidal side effects. In this model, the partial dopamine D2 receptor agonists SDZ HDC-912, SDZ HAC-911, terguride, (-)-3-(3-hydroxyphenyl)-N-propylpiperidine) ((-)-3-PPP) and SND 919 were tested for extrapyramidal side-effect liability. Their antipsychotic potential was also tested, using a dose of dextroamphetamine producing mild stereotypy and moderate motoric unrest. For comparison, the dopamine D2 receptor agonist, LY 171555 and antagonist, raclopride were used. In contrast to the other drugs tested, SDZ HAC-911 consistently reduced oral activity, P < 0.05 (at doses from 0.005 to 0.025 mg/kg). The relative dystonic potencies were raclopride > SDZ HDC-912 > SDZ HAC-911 = terguride. Neither (-)-3-PPP nor SND 919 produced dystonia, but had observable dopamine D2 receptor agonistic effects, (-)-3-PPP producing emesis at 1-4 mg/kg and SND 919 producing motoric unrest and stereotypy at 0.05-0.25 mg/kg. Comparing the antiamphetamine effects of the more antagonist-like drugs with raclopride, the relative potencies were terguride = SDZ HAC-911 > SDZ HDC-912 > raclopride. Comparing the antiamphetamine effects of the more agonist-like drugs with LY 171555, the relative potencies were SND 919 > (-)-3-PPP > LY 171555 in relation to motoric unrest, while neither (-)-3-PPP nor LY 171555 produced inhibition of stereotypy.

Administration, Oral↗

Proposed animal model of attention deficit hyperactivity disorder.

Dopamine (DA) neurons are implicated in the hyperlocomotion of neonatal 6-hydroxydopamine (6-OHDA)-lesioned rats, an animal model of attention deficit hyperactivity disorder (ADHD). Because serotonin (5-HT) neurons mediate some DA agonist effects, we investigated the possible role of 5-HT neurons on locomotor activity. Rats were treated at 3 days after birth with vehicle or 6-OHDA (134 micrograms ICV; desipramine pretreatment, 20 mg/kg IP, 1 h), and at 10 weeks with vehicle or 5,7-dihydroxytryptamine (5,7-DHT; 75 micrograms ICV; pretreatment with desipramine and pargyline, 75 mg/kg IP, 30 min), to destroy DA and/or 5-HT fibers. Intense spontaneous hyperlocomotor activity was produced in rats lesioned with both 6-OHDA and 5,7-DHT. Locomotor time in this group was 550 +/- 17 s in a 600 s session, vs. 127 +/- 13 s in the 6-OHDA group and < 75 s in 5,7-DHT and intact control groups (p < 0.001). Oral activity dose-effect curves established that 5,7-DHT attenuated DA D1 receptor supersensitivity and further sensitized 5-HT2c receptors. Acute treatment with dextroamphetamine (0.25 mg/kg SC) reduced locomotor time in 6-OHDA + 5,7-DHT-lesioned rats to 76 +/- 37 s (p < 0.001). Striatal DA was reduced by 99% and 5-HT was reduced by 30% (vs. 6-OHDA group). Because combined 6-OHDA (to neonates) and 5,7-DHT (to adults) lesions produce intense hyperlocomotion that is attenuated by amphetamine, we propose this as a new animal model of ADHD. The findings suggest that hyperactivity in ADHD may be due to injury or impairment of both DA and 5-HT neurons.

5,7-Dihydroxytryptamine↗

Amphetamine exposure is elevated in Parkinson's disease.

BACKGROUND: Since the 1930's, amphetamine drugs have been used therapeutically and recreationally. High doses are associated with acute injury to axon terminals of dopaminergic neurons. It is unknown whether low dose exposure to amphetamine over a prolonged time period is associated with the development of Parkinson's disease (PD). METHODS: A telephone survey of drug and chemical exposure was administered to patients from three faculty practice clinics at UCSF. Patients were asked to participate if they had been diagnosed with peripheral neuropathy (PN), amyotrophic lateral sclerosis (ALS), or PD between the ages of 40 and 64. Spouses or caregivers were also asked to participate. "Amphetamine exposure" was defined as a prior use of amphetamine, methamphetamine or dextroamphetamine. "Prolonged exposure" was defined as amphetamine use that occurred more than twice a week for > or =3 months or weekly usage for > or =1 year and had to occur before diagnosis of the neurological condition. RESULTS: Prolonged exposure to either prescribed or non-prescribed amphetamine was common, occurring in 15% with PN (11/76), 13% with ALS (9/72), and 11% with PD (17/158). Prolonged amphetamine exposure was more frequent in diseased patients compared to spouses when all diseases were combined (adjusted OR=3.15, 95% CI 1.42-7.00, p=0.005). When tested alone, only the Parkinson's disease group retained statistical significance (adjusted OR=8.04, 95% CI 1.56-41.4, p=0.013). For most individuals, exposure occurred long before diagnosis (averages: PN 25 years, ALS 28 years, and PD 27 years). CONCLUSIONS: The elevated rate of prolonged amphetamine exposure in PD is intriguing and bears further investigation.

Adrenergic Agents↗

Attention deficit disorder and epilepsy.

Countless studies have demonstrated that patients with epilepsy have a significant increase in behavioral disturbances of all kinds, including hyperactivity and inattention. This finding has been demonstrated in studies utilizing observer questionnaires and behavior rating scales, neuropsychological test batteries, and standardized tests of attention such as continuous performance tests. Multiple factors must be considered in the evaluation of a child with epilepsy and hyperactivity or inattention. For instance, inattention could be due to subclinical seizures, undiagnosed learning disabilities, disturbed sleep as a result of a side effect of antiepileptic medication, or due to an attention deficit disorder. Electroencephalographic monitoring is helpful to distinguish between behavioral inattention and partial complex or absence seizures. Electroencephalographic monitoring can also assess subclinical spike frequency, which may affect attention and other aspects of cognitive functioning in various ways, even in the absence of clinical seizures. Most antiepileptic drugs do not adversely affect attention and behavior in therapeutic doses, with the exception of phenobarbital, gabapentin, and topiramate. Some antiepileptic drugs, such as lamotrigine and carbamazepine, may even have beneficial effects. The preponderance of evidence suggests that stimulants other than bupropion are safe and effective in the treatment of attention deficit disorder in children with epilepsy, although controlled studies of dextroamphetamine in this population are lacking. So far, atomoxetine has not been demonstrated to have any adverse effect in children with epilepsy.

Attention Deficit Disorder with Hyperactivity↗

Trend and area variation in amphetamine prescription usage among children and adolescents in Michigan.

The increased use of stimulant medications for children and teenagers is an ongoing issue of professional and public concern. Unlike methylphenidate, the growth of prescriptions and patterns of utilization of amphetamines for pediatric populations have not been well documented. The study objectives were to describe the trends of amphetamine prescription utilization among pediatric age groups in Michigan and to compare area variations. A population-based computerized data set from the state of Michigan was used to extract all outpatient prescriptions for Schedule II amphetamines dispensed from 1990 to 1997. The prescribing rates by age groups and by counties were computed with the projected population size of corresponding years, and mapped and analyzed with spatial statistical methods. Counties that did not conform to the global spatial dependence pattern in the prescription rate were identified using Moran scatter plot. A total of 236,661 outpatient prescriptions for amphetamines were dispensed in Michigan during the time frame, including less than 1% for methamphetamine, 24.5% for amphetamine, and 74.8% for dextroamphetamine. The prescribing rate was highest among children 10-14 years old (380 prescriptions per 10,000 people) in 1997, followed by children 5-9 years old (253 prescriptions per 10,000). Over the 8-year period, the prescribing rates of amphetamines increased significantly, ranging from 380% for children 2-4 years to 817% for teenagers older than 14 years. The rates among counties ranged from 60 to 1648 per 10,000 children 5-14 years old, with the highest prescribing rates in the northwestern regions of Michigan. Although spatial dependence explained 36% of the variance, the area variations that are unaccounted for are still considerable. In conclusion, there were substantial increases and unexplained area variations in amphetamine usage in Michigan during the study period. Both phenomena require awareness and evaluation from researchers, policy makers, clinicians, and the public.

Adolescent↗

Amphetamine-induced dopamine release in human ventral striatum correlates with euphoria.

BACKGROUND: Studies in experimental animals have implicated the mesolimbic dopaminergic projections into the ventral striatum in the neural processes underlying behavioral reinforcement and motivated behavior; however, understanding the relationship between subjective emotional experience and ventral striatal dopamine (DA) release has awaited human studies. Using positron emission tomography (PET), we correlated the change in endogenous dopamine concentrations following dextroamphetamine (AMPH) administration with the associated hedonic response in human subjects and compared the strength of this correlation across striatal subregions. METHODS: We obtained PET measures of [(11)C]raclopride specific binding to DA D2/D3 receptors before and after AMPH injection (0.3 mg/kg IV) in seven healthy subjects. The change in [(11)C]raclopride binding potential (DeltaBP) induced by AMPH pretreatment and the correlation between DeltaBP and the euphoric response to AMPH were compared between the anteroventral striatum (AVS; comprised of accumbens area, ventromedial caudate, and anteroventral putamen) and the dorsal caudate (DCA) using an MRI-based region of interest analysis of the PET data. RESULTS: The mean DeltaBP was greater in the AVS than in the DCA (p <.05). The AMPH-induced changes in euphoria analog scale scores correlated inversely with DeltaBP in the AVS (r = -.95; p <.001), but not in the DCA (r =.30, ns). Post hoc assessments showed that changes in tension-anxiety ratings correlated positively with DeltaBP in the AVS (r =.80; p [uncorrected] <.05) and that similar relationships may exist between DeltaBP and emotion ratings in the ventral putamen (as were found in the AVS). CONCLUSIONS: The preferential sensitivity of the ventral striatum to the DA releasing effects of AMPH previously demonstrated in experimental animals extends to humans. The magnitude of ventral striatal DA release correlates positively with the hedonic response to AMPH.

Adult↗