Delayed yet persistent effects of daily risperidone on activity in developing rats.

Early-life administration of risperidone, the most widely used antipsychotic drug in children, leads to persistently elevated locomotor activity in adult rats. This study determined whether and when elevated locomotor activity emerges during developmental risperidone administration. Developing and adult rats were administered daily injections of risperidone (1.0 and 3.0 mg/kg) or vehicle for 4 weeks beginning at postnatal days 14 and 74, respectively. Starting with the first injection and every 7 days thereafter, locomotor activity was measured immediately after the injection and 20 min before the next day's injection. Activity was also recorded 1 week after the final injection. Risperidone markedly decreased locomotor activity in developing and adult rats immediately after injection. Within 24 h after their first injection, adult rats administered risperidone showed greater activity levels. In contrast, developing rats did not show compensatory hyperactivity until the beginning of the fourth week of risperidone administration. One week after the final risperidone injection, there was no evidence of hyperactivity in the adult rats maintained on risperidone, but developing rats administered risperidone, especially females, showed greater activity levels relative to vehicle-administered controls. In comparison with adult rats, the emergence of compensatory hyperactivity during long-term antipsychotic drug administration is delayed in developing rats, but persists after treatment cessation.

Atp13a2-deficient mice exhibit neuronal ceroid lipofuscinosis, limited α-synuclein accumulation and age-dependent sensorimotor deficits.

Mutations in ATP13A2 (PARK9), encoding a lysosomal P-type ATPase, are associated with both Kufor-Rakeb syndrome (KRS) and neuronal ceroid lipofuscinosis (NCL). KRS has recently been classified as a rare genetic form of Parkinson's disease (PD), whereas NCL is a lysosomal storage disorder. Although the transport activity of ATP13A2 has not been defined, in vitro studies show that its loss compromises lysosomal function, which in turn is thought to cause neuronal degeneration. To understand the role of ATP13A2 dysfunction in disease, we disrupted its gene in mice. Atp13a2(-/-) and Atp13a2(+/+) mice were tested behaviorally to assess sensorimotor and cognitive function at multiple ages. In the brain, lipofuscin accumulation, α-synuclein aggregation and dopaminergic pathology were measured. Behaviorally, Atp13a2(-/-) mice displayed late-onset sensorimotor deficits. Accelerated deposition of autofluorescent storage material (lipofuscin) was observed in the cerebellum and in neurons of the hippocampus and the cortex of Atp13a2(-/-) mice. Immunoblot analysis showed increased insoluble α-synuclein in the hippocampus, but not in the cortex or cerebellum. There was no change in the number of dopaminergic neurons in the substantia nigra or in striatal dopamine levels in aged Atp13a2(-/-) mice. These results show that the loss of Atp13a2 causes sensorimotor impairments, α-synuclein accumulation as occurs in PD and related synucleinopathies, and accumulation of lipofuscin deposits characteristic of NCL, thus providing the first direct demonstration that null mutations in Atp13a2 can cause pathological features of both diseases in the same organism.

Early-life risperidone alters locomotor responses to apomorphine and quinpirole in adulthood.

An escalating trend of antipsychotic drug use in children with ADHD, disruptive behavior disorder, or mood disorders has raised concerns about the impact of these drugs on brain development. Since antipsychotics chiefly target dopamine receptors, it is important to assay the function of these receptors after early-life antipsychotic administration. Using rats as a model, we examined the effects of early-life risperidone, the most prescribed antipsychotic drug in children, on locomotor responses to the dopamine D1/D2 receptor agonist, apomorphine, and the D2/D3 receptor agonist, quinpirole. Female and male Long-Evans rats received daily subcutaneous injections of risperidone (1.0 and 3.0 mg/kg) or vehicle from postnatal day 14-42. Locomotor responses to one of three doses (0.03, 0.1, and 0.3 mg/kg) of apomorphine or quinpirole were tested once a week for four weeks beginning on postnatal day 76 and 147 for each respective drug. The locomotor activity elicited by the two lower doses of apomorphine was significantly greater in adult rats, especially females, administered risperidone early in life. Adult rats administered risperidone early in life also showed more locomotor activity after the low dose of quinpirole. Overall, female rats were more sensitive to the locomotor effects of each agonist. In a separate group of rats administered risperidone early in life, autoradiography of forebrain D2 receptors at postnatal day 62 revealed a modest increase in D2 receptor density in the medial caudate. These results provide evidence that early-life risperidone administration can produce long-lasting changes in dopamine receptor function and density.

Ciproxifan, an H3 receptor antagonist, alleviates hyperactivity and cognitive deficits in the APP Tg2576 mouse model of Alzheimer's disease.

Previous research has indicated that the blockade of H(3)-type histamine receptors may improve attention and memory in normal rodents. The purpose of this study was to determine if ciproxifan, an H(3) receptor antagonist, could alleviate the hyperactivity and cognitive deficits observed in a transgenic mouse model (APP(Tg2576)) of Alzheimer's disease. APP(Tg2576) mice displayed significantly greater locomotor activity than wild-type mice, but APP(Tg2576) mice provided with daily ciproxifan treatment showed activity levels that did not differ from wild-type mice. In the swim maze, APP(Tg2576) mice exhibited significantly longer escape latencies, but the APP(Tg2576) mice treated daily with ciproxifan had latencies that were indistinguishable from controls. In probe trials conducted one hour after the last training trial, ciproxifan-treated APP(Tg2576) mice spent more time near the previous platform location and made more crossings of this area than did saline-treated APP(Tg2576) mice. APP(Tg2576) mice also demonstrated a significant impairment in the object recognition task that was reversed by acute treatment with ciproxifan (3.0mg/kg). These data support the idea that modulation of H(3) receptors represents a novel and viable therapeutic strategy in the treatment of Alzheimer's disease.

Effects of energy drinks mixed with alcohol on behavioral control: risks for college students consuming trendy cocktails.

BACKGROUND: There has been a dramatic rise in the consumption of alcohol mixed with energy drinks (AmED) in young people. AmED have been implicated in risky drinking practices and greater accidents and injuries have been associated with their consumption. Despite the increased popularity of these beverages (e.g., Red Bull and vodka), there is little laboratory research examining how the effects of AmED differ from alcohol alone. This experiment was designed to investigate if the consumption of AmED alters neurocognitive and subjective measures of intoxication compared with the consumption of alcohol alone. METHODS: Participants (n=56) attended 1 session where they were randomly assigned to receive one of 4 doses (0.65 g/kg alcohol, 3.57 ml/kg energy drink, AmED, or a placebo beverage). Performance on a cued go/no-go task was used to measure the response of inhibitory and activational mechanisms of behavioral control following dose administration. Subjective ratings of stimulation, sedation, impairment, and level of intoxication were recorded. RESULTS: Alcohol alone impaired both inhibitory and activational mechanisms of behavioral control, as evidenced by increased inhibitory failures and increased response times compared to baseline performance. Coadministration of the energy drink with alcohol counteracted some of the alcohol-induced impairment of response activation, but not response inhibition. For subjective effects, alcohol increased ratings of stimulation, feeling the drink, liking the drink, impairment, and level of intoxication, and alcohol decreased the rating of ability to drive. Coadministration of the energy drink with alcohol increased self-reported stimulation, but resulted in similar ratings of the other subjective effects as when alcohol was administered alone. CONCLUSIONS: An energy drink appears to alter some of the objective and subjective impairing effects of alcohol, but not others. Thus, AmED may contribute to a high-risk scenario for the drinker. The mix of impaired behavioral inhibition and enhanced stimulation is a combination that may make AmED consumption riskier than alcohol consumption alone.

Chronic risperidone administration leads to greater amphetamine-induced conditioned place preference.

Risperidone is an atypical antipsychotic drug used increasingly in children to manage symptoms of ADHD and conduct disorder. In rats, developmental risperidone administration is accompanied by increased locomotor activity during adulthood, as well as heightened sensitivity to the locomotor stimulating effects of amphetamine. This study compared sensitivity to the rewarding effects of amphetamine, as measured by conditioned place preference (CPP), between groups of rats administered chronic risperidone (3.0 mg/kg, s.c.) during development (postnatal days 14-42) or adulthood (postnatal days 77-105). Locomotor activity in a novel test cage and amphetamine-induced CPP were measured beginning three and four weeks, respectively, after the final risperidone injection. Female rats administered risperidone early in life were more active than any other group tested. Previous risperidone administration enhanced amphetamine CPP regardless of sex, and this effect appeared more prominent in the developmentally treated group. The density of forebrain dopamine transporters, a primary target of amphetamine, was also quantified in rats administered risperidone early in life and found to be reduced in the medial anterior, posterior, and ventral caudate nucleus. These results suggest that chronic risperidone treatment modifies later locomotor activity and sensitivity to the reinforcing effects of amphetamine, perhaps via a mechanism related to decreased forebrain dopamine transporter density.

Dopamine modulates effort-based decision making in rats.

Previous research has implicated dopamine as a modulating factor in choice behavior based on effort. The purpose of the present study was to determine the individual contribution of different dopamine receptors to effort-based decision making in rats. Rats were trained in a T-maze to choose a large-reward arm that contained 8 pellets of food over a small-reward arm that contained 2 pellets of food. The rats then were trained to climb progressively higher barriers to obtain the food from the large-reward arm. Using a discounting procedure on each test day, it was found that rats were more likely to choose the small-reward arm after treatment with the D1 antagonist, SCH-23390, or the D2 antagonist, haloperidol. The dopamine agonist, D-amphetamine, biased the rats toward choosing the large-reward arm and blunted the effects of SCH-23390 or haloperidol. Treatment with the D3 receptor antagonist, U99194, or the D3 receptor agonist, 7-OH-DPAT, did not alter choice behavior. These data indicate that D1 and D2 receptors are required for decisions based on effort.

The effects of amphetamine on working memory and locomotor activity in adult rats administered risperidone early in life.

Antipsychotic drugs are used to manage symptoms of pediatric psychiatric disorders despite the relative absence of research regarding the long-term effects of these drugs on brain development. Using rats as a model, research has demonstrated that administration of the antipsychotic drug, risperidone, during early postnatal development elevates locomotor activity and sensitivity to the locomotor effects of amphetamine during adulthood. Because risperidone targets neurotransmitter receptors and forebrain regions associated with working memory, the present study determined whether early-life risperidone altered working memory during adulthood and its sensitivity to amphetamine-induced impairment. Female and male rats received subcutaneous (sc) injections of risperidone daily on postnatal days 14-42. Early-life risperidone increased spontaneous locomotor activity and amphetamine-induced hyperactivity during adulthood, although the effects were significantly greater in females. Working memory was tested in an operant-based, delayed non-matching-to-sample task. Early-life risperidone did not affect the percentage of correct choices observed during sessions with 0-8 second delays but impaired performance during sessions with 0-24 second delays. In a subsequent set of tests using 0-24 second delays, amphetamine (0.75 and 1.25 mg/kg, sc) significantly reduced the percentage of correct choices at most delays, but risperidone did not exacerbate this effect. These data suggest that early-life risperidone leads to modest deficits in working memory during adulthood, but does not alter the perturbation of working memory by amphetamine.

Ataxia and paroxysmal dyskinesia in mice lacking axonally transported FGF14.

Fibroblast growth factor 14 (FGF14) belongs to a distinct subclass of FGFs that is expressed in the developing and adult CNS. We disrupted the Fgf14 gene and introduced an Fgf14(N-beta-Gal) allele that abolished Fgf14 expression and generated a fusion protein (FGF14N-beta-gal) containing the first exon of FGF14 and beta-galactosidase. Fgf14-deficient mice were viable, fertile, and anatomically normal, but developed ataxia and a paroxysmal hyperkinetic movement disorder. Neuropharmacological studies showed that Fgf14-deficient mice have reduced responses to dopamine agonists. The paroxysmal hyperkinetic movement disorder phenocopies a form of dystonia, a disease often associated with dysfunction of the putamen. Strikingly, the FGF14N-beta-gal chimeric protein was efficiently transported into neuronal processes in the basal ganglia and cerebellum. Together, these studies identify a novel function for FGF14 in neuronal signaling and implicate FGF14 in axonal trafficking and synaptosomal function.

The effects of clonidine on discrete-trial delayed spatial alternation in two rat models of memory loss.

Spatial memory impairments observed in Alzheimer's disease and schizophrenia have been attributed to many factors, including glutamate hypofunction and reduced hippocampal volume. Clonidine, a non-specific alpha(2) adrenergic receptor agonist, improves spatial memory in animals treated with the N-methyl-D-aspartate (NMDA) receptor antagonist, phencyclidine; however, its effects on memory deficits produced by other NMDA antagonists or hippocampal damage have not been fully characterized. The purpose of this study was to determine if clonidine could alleviate memory deficits produced by the NMDA antagonist, MK-801, or by excitotoxic hippocampal damage. In the first phase of the study, male rats were pretreated with clonidine (0.01 or 0.05 mg/kg) or saline, and treated with MK-801 (0.1 mg/kg) or saline prior to discrete-trial delayed alternation or radial-arm maze testing. MK-801 impaired delayed alternation performance and increased the number of arm revisits in the radial-arm maze. Clonidine pretreatment significantly alleviated these drug-induced deficits. In the second phase of the study, excitotoxic damage was produced in the dorsal hippocampus with NMDA. Hippocampal damage produced a significant impairment in the delayed alternation task, yet pretreatment with clonidine did not alleviate this damage-induced deficit. Taken together, the data indicate that clonidine alleviates memory impairments produced by glutamate hypofunction, but not by hippocampal damage. This caveat may be important in designing treatments for memory disorders not linked to a single pathophysiological mechanism.

Magnesium deficiency reduces fear-induced conditional lick suppression in mice.

The consequences of broad-scale alterations in magnesium (Mg2+) levels on learning and memory are poorly understood. We have recently demonstrated that adult male mice maintained on an Mg2+-deficient diet exhibit reduced conditional freezing behavior. The purpose of the present study was to determine if the detrimental effect of Mg2+ deficiency in mice extended to another measure of conditional fear, conditioned lick suppression (CLS), as well as to another form of learning, spatial learning in the swim maze task. Adult male C57Bl/6J mice were provided with a normal or Mg2+-deficient diet and were trained and tested ten days later for conditional fear, using CLS and freezing as indicators of learning. Learning in the swim maze was tested in a separate cohort of mice during days 14-18 of diet exposure. Mg2+-deficient mice showed reduced CLS as well as conditional freezing behavior in comparison to control mice. However, learning in the swim maze task was normal in Mg2+-deficient mice. These studies indicate that the detrimental effects of Mg2+ deficiency extend to other measures of conditional fear but not to all forms of learning.

Early-life risperidone enhances locomotor responses to amphetamine during adulthood.

Antipsychotic drug prescriptions for pediatric populations have increased over the past 20 years, particularly the use of atypical antipsychotic drugs such as risperidone. Most antipsychotic drugs target forebrain dopamine systems, and early-life antipsychotic drug exposure could conceivably reset forebrain neurotransmitter function in a permanent manner that persists into adulthood. This study determined whether chronic risperidone administration during development modified locomotor responses to the dopamine/norepinephrine agonist, D-amphetamine, in adult rats. Thirty-five male Long-Evans rats received an injection of one of four doses of risperidone (vehicle, .3, 1.0, 3.0mg/kg) each day from postnatal day 14 through 42. Locomotor activity was measured for 1h on postnatal days 46 and 47, and then for 24h once a week over the next two weeks. Beginning on postnatal day 75, rats received one of four doses of amphetamine (saline, .3, 1.0, 3.0mg/kg) once a week for four weeks. Locomotor activity was measured for 27h after amphetamine injection. Rats administered risperidone early in life demonstrated increased activity during the 1 and 24h test sessions conducted prior to postnatal day 75. Taking into account baseline group differences, these same rats exhibited significantly more locomotor activity in response to the moderate dose of amphetamine relative to controls. These results suggest that early-life treatment with atypical antipsychotic drugs, like risperidone, permanently alters forebrain catecholamine function and increases sensitivity to drugs that target such function.

Effects of risperidone on locomotor activity and spatial memory in rats with hippocampal damage.

Hippocampal damage produces spatial memory impairment and hyperactivity in animals, while reductions in hippocampal size have been associated with memory deficits in humans. There are no known treatments for the behavioral changes specifically related to reduced hippocampal size. The purpose of this study was to determine if risperidone, an atypical antipsychotic drug that has shown cognitive-enhancing properties in animals and humans, could alleviate the behavioral disturbances produced by hippocampal damage in rats. Young adult male Sprague-Dawley rats received either sham stereotaxic surgery or direct stereotaxic infusions of N-methyl-d-aspartate (NMDA) into the dorsal hippocampus to produce hippocampal damage. One week later, animals in each group received daily subcutaneous injections of either saline or risperidone (0.2mg/kg) until the end of the experiment. Three weeks after surgery, locomotor activity was tested in all animals. During the fourth and fifth post-surgical weeks, animals were tested in a discrete-trial, delayed rewarded alternation memory paradigm. Risperidone reversed lesion-induced hyperactivity; however it also decreased activity in the sham control rats. In the delayed alternation task, there were significant drug and lesion effects irrespective of the day of testing, but there was no drugxlesion interaction. Hippocampal lesions impaired performance in the delayed alternation task in saline and risperidone-treated rats. However, risperidone modestly improved performance in lesioned and sham controls in comparison to saline-treated lesioned and sham controls. Risperidone also slowed choice time in the alternation task. These data indicate that risperidone does not specifically correct the neurobiological consequences of hippocampal damage, but that animals with hippocampal damage nonetheless maintain a significant degree of sensitivity to the beneficial effects of risperidone.

Magnesium deficiency impairs fear conditioning in mice.

Magnesium (Mg2+) is one of the most abundant cations found in the body. In the central nervous system, Mg2+ plays an important role in the function of N-methyl-D-aspartate (NMDA)-type glutamate receptors, which are centrally involved in memory processing. Despite the relatively large concentration of Mg2+ in the CNS, little is known about the behavioral consequences of Mg2+ deficiency. The purpose of this study was to address this issue by assessing fear conditioning and related behaviors in mice maintained on normal or Mg(2+)-deficient diets. Young adult male C57Bl/6J mice were placed on a control or Mg(2+)-deficient diet, and testing was conducted between 10 and 21 days later. Magnesium-deficient mice exhibited impairments in contextual and cued fear conditioning. These impairments could not be attributed to changes in locomotor activity, exploration, or pain sensitivity. Furthermore, Mg(2+)-deficient mice were more sensitive to the convulsant effects of a peripheral injection of NMDA (100 mg/kg, IP). The results suggest that magnesium deficiency can lead to specific impairments in emotional memory. Such impairments may be related to hypersensitivity of NMDA-type glutamate receptors in Mg(2+)-deficient mice.

Comparison of Neurological Function in Males and Females from Two Substrains of C57BL/6 Mice.

The C57BL/6 (B6) mouse is the background strain most frequently used for genetically-modified mice. Previous studies have found significant behavioral and genetic differences between the B6J (The Jackson Laboratory) and B6N substrains (National Institutes of Health); however, most studies employed only male mice. We performed a comprehensive battery of motor function and learning and memory tests on male and female mice from both substrains. The B6N male mice had greater improvement in the rotarod test. In contrast, B6J female mice had longer latencies to falling from the rotarod. In the Morris water maze (MWM), B6J males had significantly shorter latencies to finding the hidden platform. However, B6N females had significantly shorter path lengths in the reversal and shifted-reduced phases. In open field locomotor activity, B6J males had higher activity levels, whereas B6N females took longer to habituate. In the fear conditioning test, B6N males had a significantly longer time freezing in the new context compared with B6J males, but no significant differences were found in contextual or cued tests. In summary, our findings demonstrate the importance of testing both males and females in neurobehavioral studies. Both factors (sex and substrain) must be taken into account when designing developmental neurotoxicology studies.

Early-life risperidone administration alters maternal-offspring interactions and juvenile play fighting.

Risperidone is an antipsychotic drug that is approved for use in childhood psychiatric disorders such as autism. One concern regarding the use of this drug in pediatric populations is that it may interfere with social interactions that serve to nurture brain development. This study used rats to assess the impact of risperidone administration on maternal-offspring interactions and juvenile play fighting between cage mates. Mixed-sex litters received daily subcutaneous injections of vehicle or 1.0 or 3.0mg/kg of risperidone between postnatal days (PNDs) 14-42. Rats were weaned and housed three per cage on PND 21. In observations made between PNDs 14-17, risperidone significantly suppressed several aspects of maternal-offspring interactions at 1-hour post-injection. At 23 h post-injection, pups administered risperidone had lower activity scores and made fewer non-nursing contacts with their moms. In observations of play-fighting behavior made once a week between PNDs 22-42, risperidone profoundly decreased many forms of social interaction at 1h post-injection. At 23h post-injection, rats administered risperidone made more non-social contacts with their cage mates, but engaged in less social grooming. Risperidone administration to rats at ages analogous to early childhood through adolescence in humans produces a pattern of abnormal social interactions across the day that could impact how such interactions influence brain development.

The effects of excitotoxic hippocampal lesions in rats on risperidone- and olanzapine-induced locomotor suppression.

Previous studies have shown that excitotoxic hippocampal lesions in rats attenuate the ability of different doses of haloperidol, but not of clozapine, to suppress locomotor activity. The purpose of the present study was to determine if kainic acid-induced hippocampal damage reduces the degree of locomotor suppression produced by two relatively newer antipsychotic drugs, risperidone and olanzapine. Young adult male rats received bilateral intracerebroventricular infusions of the excitotoxin, kainic acid (KA), or vehicle and were tested for locomotor responses to drug treatment 30 days later. Infusions of KA produced neuronal loss in the CA3 region of the dorsal hippocampus in every rat. As reported previously, KA lesions reduced the ability of haloperidol (0.35 mg/kg) to completely suppress the locomotor activity elicited by amphetamine (1.5 mg/kg) relative to the effect of haloperidol in non-lesioned controls. Lesioned animals treated with a moderate dose of risperidone (1.4 mg/kg) also exhibited significantly more locomotor activity after amphetamine treatment in comparison to control animals. A trend toward greater activity was also observed in the lesioned group relative to the control group after olanzapine (3.0 mg/kg) injection (p =.09, 2-tailed). The locomotor effects of lower and higher doses of risperidone and olanzapine were not altered by kainic acid lesions. These data suggest that the locomotor-suppressive effects of moderate doses of risperidone and, perhaps, olanzapine involve hippocampal neurons, but that higher doses of each drug can suppress activity in a hippocampal-independent manner.

NMDA receptor blockade and hippocampal neuronal loss impair fear conditioning and position habit reversal in C57Bl/6 mice.

The interpretation of learning and memory deficits in transgenic mice has largely involved theories of NMDA receptor and/or hippocampal function. However, there is little empirical data that describes what NMDA receptors or the hippocampus do in mice. This research assessed the effects of different doses of the NMDA receptor antagonist, MK-801, or different-sized hippocampal lesions on several behavioral parameters in adult male C57Bl/6 mice. In the first set of experiments, different doses of MK-801 (0.05-0.3mg/kg, s.c.) were assayed in fear conditioning, shock sensitivity, locomotion, anxiety, and position habit reversal tests. Contextual and cued fear conditioning, and position habit reversal were impaired in a dose-dependent manner. Locomotor activity was increased immediately after injection of the highest dose of MK-801. A second set of experiments determined the behavioral effects of a moderate and large excitotoxic hippocampal lesion. Both lesions impaired contextual conditioning, while the larger lesion interfered with cued conditioning. Reversal learning was significantly diminished by the large lesion, while the moderate lesion had a detrimental effect at a trend level (P<0.10). These results provide important reference data for studies involving genetic manipulations of NMDA receptor or hippocampal function in mice. Furthermore, they serve as a basis for a non-transgenic mouse model of the NMDA receptor or hippocampal dysfunction hypothesized to occur in human cognitive disorders.

Glucose metabolism in the amygdala in depression: relationship to diagnostic subtype and plasma cortisol levels.

In a previous positron emission tomography (PET) study of major depression, we demonstrated that cerebral blood flow was increased in the left amygdala in unipolar depressives with familial pure depressive disease (FPDD) relative to healthy controls [J. Neurosci. 12 (1992) 3628.]. These measures were obtained from relatively low-resolution PET images using a stereotaxic method based upon skull X-ray landmarks. The current experiments aimed to replicate and extend these results using higher-resolution glucose metabolism images and magnetic resonance imaging (MRI)-based region-of-interest (ROI) analysis. The specificity of this finding to FPDD was also investigated by assessing depressed samples with bipolar disorder (BD-D) and depression spectrum disease (DSD). Finally, the relationship between amygdala metabolism and plasma cortisol levels obtained during the scanning procedure was assessed. Glucose metabolism was measured using PET and 18F-fluorodeoxyglucose (18FDG) in healthy control (n=12), FPDD (n=12), DSD (n=9) and BD-D (n=7) samples in the amygdala and the adjacent hippocampus. The left amygdala metabolism differed across groups (P<.001), being increased in both the FPDD and BD-D groups relative to the control group. The left amygdala metabolism was positively correlated with stressed plasma cortisol levels in both the unipolar (r=.69; P<.005) and the bipolar depressives (r=0.68;.1

Subjective State, Blood Pressure, and Behavioral Control Changes Produced by an "Energy Shot"

Background: Energy drinks and energy shots are popular consumer beverages that are advertised to increase feelings of alertness. Typically, these products include high levels of caffeine, a mild psychostimulant drug. The scientific evidence demonstrating the specific benefits of energy products to users in terms of subjective state and objective performance is surprisingly lacking. Moreover, there are rising health concerns associated with the use of these products. Therefore, the purpose of this study was to investigate the acute effects of a popular energy shot (5-Hour Energy®) on subjective and objective measures that were assessed hourly for 6 hours following consumption. Methods: Participants (n=14) completed a three-session study where they received the energy shot, a placebo control, and no drink. Following dose administration, participants completed subjective Profile of Mood States ratings hourly for 6 hours. Participants also repeatedly completed a behavioral control task (the cued go/no-go task) and provided blood pressure and pulse rate readings at each hour. Results: Consumption of the energy shot did improve subjective state, as measured by increased ratings of vigor and decreased ratings of fatigue. However, the energy shot did not alter objective performance, which worsened over time. Importantly, the energy shot elevated both systolic and diastolic blood pressure. Conclusions: Consumption of one energy shot may only result in modest benefits to subjective state. Individuals with preexisting hypertension or other medical conditions should be cautious about using these new consumer products.