Biomedical subjects

H Scott Swartzwelder

Publications and source records attributed to H Scott Swartzwelder.

At least 19 recordsLinked to original sources

PubMed2007

Differential anxiogenic, aversive, and locomotor effects of THC in adolescent and adult rats.

RATIONALE: Unpleasant side effects of drugs of abuse often limit their repeated use; however, such effects may be attenuated in adolescents compared to adults. OBJECTIVES: We investigated whether the anxiogenic, aversive, or locomotor effects of delta-9-tetrahydrocannabinol (THC) differ between adolescent and adult rats. METHODS: We used the elevated plus maze (EPM) and light-dark tests of anxiety, the conditioned taste aversion and conditioned place aversion (CPA) tests of generalized aversion, and measures of stress hormone levels in serum to examine effects of THC in adolescent and adult rats. Locomotor activity was also recorded in the EPM, light-dark task, and CPA association sessions. RESULTS: In the EPM and light-dark tasks, THC was anxiogenic in both age groups, but the drug was more anxiogenic in adults than in adolescents. In the place and taste aversion tasks, THC was aversive in both ages, and at 1.25 and 5 mg/kg, was more aversive in adults than in adolescents. The locomotor response to THC, as measured in the anxiety tasks and CPA, affected adults more than adolescents. Multiple measures revealed a locomotor-decreasing effect in adults, whereas some measures suggested a small locomotor-increasing effect in adolescent rats. CONCLUSIONS: These results suggest that THC can have greater anxiogenic, aversive, and locomotor-reducing effects in adult rats than in adolescent rats. These findings suggest an explanation for reduced marijuana use in adult humans compared to teenagers.

Adrenocorticotropic Hormone↗

PubMed2006

Transformation of mu-opioid receptor agonists into biologically potent mu-opioid receptor antagonists.

N-Allylation (-CH(2)-CHCH(2)) of [Dmt(1)]endomorphins yielded the following: (i) [N-allyl-Dmt(1)]endomorphin-2 (Dmt=2',6'-dimethyl-l-tyrosine) (12) and [N-allyl-Dmt(1)]endomorphin-1 (15) (K(i)mu=0.45 and 0.26nM, respectively) became mu-antagonists (pA(2)=8.59 and 8.18, respectively) with weak delta-antagonism (pA(2)=6.32 and 7.32, respectively); (ii) intracerebroventricularly administered 12 inhibited morphine-induced CNS-mediated antinociception in mice [AD(50) (0.148ng/mouse) was 16-fold more potent than naloxone], but not spinal antinociception, and (iii) 15 reversed the alcohol-elevated frequency in spontaneous inhibitory post-synaptic currents (IPSC) in hippocampal CA1 pyramidal cells in rat brain slices (P=0.0055). Similarly, N-allylation of the potent mu-opioidmimetic agonists, 1,6-bis-[H-Dmt-NH]-hexane and 3,6-bis-[Dmt-NH-propyl]-2(1H)-pyrazinone, converted them into mu-antagonists (pA(2)=7.23 and 7.17 for the N-allyl-derivatives 17 and 19, respectively), and exhibited weak delta-antagonism. Thus, N-allylation of Dmt containing opioid peptides or opioidmimetics continues to provide a facile means to convert selective mu-opioid agonists into potent mu-opioid antagonists.

Alkylation↗

PubMed2006

Sedative and GABAergic effects of ethanol on male and female rats.

BACKGROUND: Women consume less alcohol than men, and yet they are more susceptible than men to the negative medical consequences of alcohol use, such as cirrhosis of the liver, cardiac disease, and cognitive impairments. This sex difference is also reflected in animal studies, in which male and female rats differ on both behavioral and electrophysiological measures. Given that one significant difference between males and females is the cycling fluctuations of the sex hormones, this study aimed to compare the relative sensitivity of adolescent and adult rats of both sexes and varying estrous stages to the behavioral and electrophysiological effects of ethanol. METHODS: Adult female rats were lavaged daily for estrous cycle assessment. Following administration of 5 g/kg ethanol, adolescent and adult male and female animals were observed for loss of the righting reflex. Then, using whole-cell recording, we tested the response of spontaneous, gamma-aminobutyric acid (GABA(A)) receptor-mediated inhibitory postsynaptic currents (sIPSCs) in hippocampal slices from drug-naïve adult male and female rats. RESULTS: Consistent with previous findings, adolescent animals were less sensitive than adults to the effect of ethanol on the righting reflex. In addition, adult proestrous and diestrous female rats were less sensitive than male rats to the sedative effects of ethanol. Finally, ethanol increased the frequency of sIPSCs in hippocampal pyramidal neurons and did so more potently in cells from male rats than in those from female rats. CONCLUSIONS: Female animals are less sensitive to the behavioral sedative effects of ethanol than adult male rats, and the effect is pronounced in the proestrous and diestrous states. This sex difference may be related to differential sensitivity of GABA receptor-mediated central nervous system function to ethanol in females.

Age Factors↗

PubMed2005

Age-related effects of alcohol on memory and memory-related brain function in adolescents and adults.

As detailed in this brief review, there is now clear evidence that adolescence represents a unique stage of brain development. Changes in brain organization and function during adolescence are widespread, and include intense rewiring in the frontal lobes and other neorcortical regions, as well as changes in a litany of subcortical structures. Recent research suggests that, because of these changes in brain function, drugs like alcohol affect adolescents and adults differently. The available evidence, much of it from research with animal models, suggests that adolescents might be more sensitive than adults to the memory impairing effects of alcohol, as well as the impact of alcohol on the brain function that underlies memory formation. For instance, when treated with alcohol, adolescent rats perform worse than adults in spatial learning tasks that are known to require the functioning of the hippocampus. Alcohol disrupts hippocampal function, and does so more potently in adolescents than adults. In contrast, adolescents appear to be far less sensitive than adults to both the sedative and motor impairing effects of alcohol. While research on this topic is still in its infancy, the findings clearly suggest that adolescence represents a unique stage of sensitivity to the impact of alcohol on behavior and brain function.

Adolescent↗

PubMed2005

Adolescence: booze, brains, and behavior.

This article represents the proceedings of a symposium at the 2004 Research Society on Alcoholism meeting in Vancouver, British Columbia, Canada, organized and chaired by Peter M. Monti and Fulton T. Crews. The presentations and presenters were (1) Introduction, by Peter M. Monti; (2) Adolescent Binge Drinking Causes Life-Long Changes in Brain, by Fulton T. Crews and Kim Nixon; (3) Functional Neuroimaging Studies in Human Adolescent Drinkers, by Susan F. Tapert; (4) Abnormal Emotional Reactivity as a Risk Factor for Alcoholism, by Robert Miranda, Jr.; (5) Alcohol-Induced Memory Impairments, Including Blackouts, and the Changing Adolescent Brain, by Aaron M. White and H. Scott Swartzwelder; and (6) Discussion, by Kenneth Sher.

Adolescent↗

PubMed2005

College students lack knowledge of standard drink volumes: implications for definitions of risky drinking based on survey data.

BACKGROUND: College students tend to pour single servings of beer and liquor that are larger than commonly used standards. The reasons for this are unknown. Students might overpour because they lack knowledge of standard serving sizes. Alternatively, they might know how much alcohol to pour but simply have difficulty pouring the correct amounts. Misperceptions of standard serving sizes could lead to inaccuracies in self-reported consumption. If this is the case, then the validity of students' responses on alcohol surveys and the definitions of risky drinking that are based on them would be called into question. This study examined how college students define standard drinks, whether their definitions are similar to the definitions commonly used by alcohol researchers and government agencies, and whether their definitions of standard drinks are related to the sizes of the drinks that they pour. The study also examined whether feedback regarding the accuracy of their definitions of standard drinks leads students to alter their self-reported levels of consumption. METHODS: Students (N = 133) completed an alcohol survey and performed tasks that required them to free-pour a single beer, glass of wine, shot of liquor, or the amount of liquor in a mixed drink. Roughly half of the students received feedback regarding their definitions of standard drinks. All students then were resurveyed about their recent levels of consumption. RESULTS: With the exception of beer, students incorrectly defined the volumes of standard servings of alcohol, overestimating the appropriate volumes. They also overestimated appropriate volumes when asked to free-pour drinks. Positive relationships existed between students' definitions of standard drinks and the sizes of the drinks that they free-poured. Feedback regarding misperceptions of standard drink volumes led to an increase in levels of self-reported consumption, suggesting that students' original estimates of their alcohol consumption were too low. CONCLUSIONS: Despite the recent focus on alcohol education and prevention at the college level, college students have not been taught how to define standard drinks accurately. They tend to overstate the appropriate volumes, leading them to overpour drinks and underreport levels of consumption. Self-reported consumption levels are altered by feedback regarding the accuracy of students' definitions of standard drinks. The findings raise important questions about the validity of students' responses on alcohol surveys and the definitions of risky drinking that are based them.

Adolescent↗

PubMed2005

Adolescent vulnerabilities to chronic alcohol or nicotine exposure: findings from rodent models.

This article presents an overview of the proceedings from a symposium entitled "Is adolescence special? Possible age-related vulnerabilities to chronic alcohol or nicotine exposure," organized by Susan Barron and Linda Spear and held at the 2004 Research Society on Alcoholism Meeting in Vancouver, British Columbia. This symposium, co-sponsored by the Fetal Alcohol Syndrome Study Group and the Neurobehavioral Teratology Society, focused on our current knowledge regarding the long-term consequences of ethanol and/or nicotine exposure during adolescence with the emphasis on data from rodent models. The support from these two societies represents the understanding by these research groups that adolescence represents a unique developmental stage for the effects of chronic drug exposure and also marks an age in which many risky behaviors including alcohol consumption and smoking typically begin. The speakers included (1) Aaron White, who presented data on the effects of adolescent ethanol exposure on subsequent motor or cognitive response to an ethanol challenge in adulthood; (2) Richard Bell, who presented data suggesting that genetic differences could play a role in adolescent vulnerability to ethanol; (3) Craig Slawecki, who presented data looking at the effects of chronic exposure to alcohol or nicotine on neurophysiologic and behavioral end points; and (4) Ed Levin, who presented data on acute and long-term consequences of adolescent nicotine exposure. Finally, Linda Spear provided some summary points and recommendations regarding unresolved issues and future directions.

Adolescent↗

PubMed2004

Experiential aspects of alcohol-induced blackouts among college students.

Our current understanding of alcohol-induced memory blackouts is derived largely from research with middle-aged, hospitalized, male alcoholics. In the present study, 50 undergraduate students (34 female and 16 male) with a history of at least one blackout were interviewed to gain insight into their experiences. Fragmentary blackouts, in which memory for events is fragmented, were far more common than blackouts of the en bloc type, in which a period of time is simply missing from memory. Most students recalled bits and pieces of events without cueing from others, yet still relied on friends, most also intoxicated themselves during the blackout period, to tell them what transpired. Thinking about the fragments triggered further recall in the majority of cases. Half of all subjects, more females than males, reported having been frightened by their last blackout experience. Being frightened typically led to more careful drinking for several weeks or longer. Characteristics of blackouts among college students in the present study are compared to the standard model of blackouts based on reports from alcoholics.

Adolescent↗

PubMed2004

Executive functioning early in abstinence from alcohol.

BACKGROUND: Executive dysfunction is among the cognitive impairments that may persist after abstinence in alcohol-dependent persons. The type(s) and extent of executive dysfunction early in abstinence have not been well characterized, but they may have important implications for the evolution of behavioral treatment strategies. METHODS: To determine which aspects of executive functioning were impaired in early abstinence, we administered memory and executive function tests to veterans who successively presented for treatment at an outpatient substance abuse clinic. We then compared the neuropsychological performance of these recovering alcoholics (n = 27) with that of age-matched primary care outpatients (n = 18). We also examined group differences in self-evaluation of cognitive decline and evaluated associations between drinking history and cognitive impairment in the index group. RESULTS: We found that the normal and alcohol-dependent groups differed on abstract reasoning, memory discrimination, and effectiveness on timed tasks. Patients in the alcohol-dependent sample were also more likely to perceive themselves as cognitively impaired. It is interesting to note that the duration of alcohol use did not relate to neuropsychological test performance, but recent quantity consumed and days of sobriety were associated with nonverbal abstract reasoning ability. CONCLUSIONS: Executive functions are impaired early in abstinence and should, therefore, be taken into account when early behavioral treatments are being developed.

Alcoholism↗

PubMed2004

Hippocampal function during adolescence: a unique target of ethanol effects.

Behaviors mediated by the hippocampus have long been known to be sensitive to the acute, chronic, and prenatal effects of ethanol. It has recently become clear that hippocampal function is uniquely responsive to ethanol during periadolescent development, and that alcohol affects behavior and brain function differently in adolescents and adults. We have used behavioral techniques, as well as extracellular and whole-cell electrophysiological techniques, to assess the effects of acute and chronic ethanol exposure on hippocampal function during adolescence and adulthood. Our results are consistent with the view that the hippocampus is more sensitive to the acute effects of ethanol during adolescence and may be more susceptible to the neurotoxic effects of ethanol during this developmental period. Studies of this type have yielded valuable information for prevention, education, and public policy efforts related to underage drinking.

Adolescent↗

PubMed2004

Predictors of relapse during treatment and treatment completion among marijuana-dependent adolescents in an intensive outpatient substance abuse program.

The present study assessed possible predictors of relapse while in treatment and treatment completion among marijuana-dependent adolescents (N = 59) in an intensive outpatient substance abuse treatment program. Comorbid depression was associated with an increased likelihood of relapse and a higher total number of relapses. As expected, relapse while in treatment was associated with a reduced likelihood of successfully completing the treatment program. Comorbid attention deficit hyperactivity disorder (ADHD) was also associated with a lower likelihood of successful program completion. These findings add to a slowly growing literature regarding adolescent substance abuse treatment, and may help clinicians identify marijuana-dependent adolescents at greater risk of relapse or noncompliance.

Adolescent↗

PubMed2003

Dietary prenatal choline supplementation alters postnatal hippocampal structure and function.

Choline, a compound present in many foods, has recently been classified as an essential nutrient for humans. Studies with animal models indicate that the availability of choline during the prenatal period influences neural and cognitive development. Specifically, prenatal choline supplementation has been shown to enhance working memory and hippocampal long-term potentiation (LTP) in adult offspring. However, the cellular mechanisms underlying these effects remain unclear. Here we report that choline supplementation, during a 6-day gestational period, results in greater excitatory responsiveness, reduced slow afterhyperpolarizations (sAHPs), enhanced afterdepolarizing potentials (ADPs), larger somata, and greater basal dendritic arborization among hippocampal CA1 pyramidal cells studied postnatally in juvenile rats (20-25 days of age). These data indicate that dietary supplementation with a single nutrient, choline, during a brief, critical period of prenatal development, alters the structure and function of hippocampal pyramidal cells.

Action Potentials↗

PubMed2003

Adolescent-onset nicotine self-administration modeled in female rats.

RATIONALE: Although the great majority of tobacco addiction begins during adolescence, little is known about differential nicotine effects in adolescents versus adults. OBJECTIVES: A rat model was used to determine the impact of the age of onset on nicotine self-administration. METHODS: In expt 1, nicotine self-administration of female Sprague-Dawley rats over a range of acute doses (0.01-0.08 mg/kg per infusion) was determined in adolescent (beginning at 54-62 days) versus adult (beginning at 84-90 days). In expt 2, chronic nicotine self-administration over 4 weeks from adolescence into adulthood was compared with the chronic self-administration beginning in adulthood. In expt 3, adolescent-adult differences in nicotine effects on body temperature and locomotor responses were determined. RESULTS: Adolescent-onset rats showed a significant main effect of increased nicotine intake compared with adult-onset rats in an eight-fold range of acute unit doses/infusion. Significant age differences were also seen in the chronic level of nicotine self-administration. Over 4 weeks, the adolescent-onset group had nearly double the rate of nicotine self-administration of the benchmark nicotine dose (0.03 mg/kg per infusion) compared to the adult-onset group. This increased nicotine intake persisted into adulthood. Adolescent rats had significantly greater response than adults to the hypothermic effects of nicotine, but had significantly less response than adults to the reduction in locomotor activity seen after nicotine. CONCLUSIONS: Adolescent-onset nicotine self-administration in female rats was associated with significantly higher levels of nicotine self-administration versus rats, which began nicotine self-administration in adulthood. This greater self-administration persists into adulthood and may underlie greater propensity of adolescents to nicotine addiction.

Adolescent↗

PubMed2003

Prenatal dietary choline availability alters postnatal neurotoxic vulnerability in the adult rat.

The availability of choline during the prenatal period influences neural and cognitive development. Here we report that choline supplementation during a six-day gestational period protects against neurodegeneration in the posterior cingulate and retrosplenial cortices of adult female rats produced by systemic administration of the N-methyl-D-aspartate receptor antagonist dizocilpine (MK-801). These data show that availability of choline during a brief prenatal period diminishes vulnerability to neurotoxicity in adult offspring.

Animals↗

PubMed2003

Performance of recently detoxified patients with alcoholism on a neuropsychological screening test.

OBJECTIVE: Early in recovery from alcoholism, cognitive deficits may compromise patients' utilization of rehabilitative information. Cognitive impairment in a sample of newly detoxified inpatients with alcoholism was examined using the Neurobehavioral Cognitive Status Examination (NCSE). METHODS: Consecutively admitted psychiatric inpatients (N=233) with an alcohol-related primary diagnosis (63% male, mean age 46.3) were administered the NCSE following medical stabilization. Within-samples differences between age and diagnostic groups were examined and scores were compared to normative samples. RESULTS: Inpatients older than 50 demonstrated significant cognitive deficits for all scales except Attention. In comparison with normative samples, patients with alcoholism produced lower scores, with the most pronounced deficits among middle-aged patients. In alcohol-abusing patients with medical comorbidities, language deficits and more severe memory deficits were observed. Abuse severity or comorbid psychiatric disorder produced no differences in NCSE scores. CONCLUSIONS: Neuropsychological screening following detoxification in patients diagnosed with an alcohol disorder reflected the effects of increased age and medical comorbidity. Our finding of frequent deficits in abstraction, comprehension, and memory suggests that cognitive-behavioral treatments for inpatients may be less effective if cognitive impairment is not considered.

Adolescent↗

PubMed2003

Do college students drink more than they think? Use of a free-pour paradigm to determine how college students define standard drinks.

RATIONALE: Much of what is known about college drinking comes from self-report survey data. Such surveys typically ask students to indicate how many drinks they consume within a given period of time. It is currently unclear whether college students and researchers use similar operational definitions of a single drink. This information is critical given the widespread reliance on survey data for assessing the correlates and consequences of college drinking. OBJECTIVES: This study investigated whether college students define standard drink volumes in a way that is consistent with the operational definitions commonly used by researchers. METHODS: Students (n = 106) were administered an alcohol survey and then asked to perform three tasks. The tasks involved free-pouring fluid into empty cups of different sizes and estimating the volume of a single beer, a shot of liquor, or the amount of liquor in a mixed drink. The volumes poured by students then were compared with standards used in a well-known nationwide survey (i.e., 12 oz of beer and 1.25 oz of liquor in a shot or mixed drink). RESULTS: In every cup size of every task, students overestimated how much fluid they should pour to create a standard drink. In all three tasks, the magnitude of the discrepancy increased with cup size. Collapsed across cup sizes, students overpoured shots by 26%, mixed drinks by 80%, and beer by 25%. When a more liberal serving size of liquor (1.5 oz) was used as the standard, the results of the mixed drink task remained unchanged. However, the volumes poured by students during the shot free-pour task differed from the standard in only one cup size. CONCLUSIONS: The data suggest that college students drink more alcohol than indicated by their survey responses, raising questions about the validity of widely used alcohol surveys. Efforts to educate students about the alcohol content of standard drinks should be enhanced.

Adolescent↗

PubMed2002

Prenatal choline supplementation protects against postnatal neurotoxicity.

Choline, a dietary compound present in many foods, has recently been classified as an essential nutrient for humans. There is evidence from animal models that the availability of choline during the prenatal period influences neural and cognitive development. Here we report that choline supplementation during a 6 d gestational period protects against neurodegeneration in the posterior cingulate and retrosplenial cortices of female adolescent rats produced by peripheral administration of the NMDA receptor antagonist dizocilpine (MK-801). These data show that availability of a single nutrient, choline, during a brief period of prenatal development diminishes vulnerability to neurotoxicity in adolescent offspring.

Aging↗

PubMed2002

Cognitive deficits and CNS damage after a 4-day binge ethanol exposure in rats.

Impairments of learning and memory are common neuropsychological sequelae of chronic alcohol abuse. Alcoholics often have impairments of anterograde memory, including spatial memory dysfunction, and a tendency toward response perseveration. This study was designed to assess the effects of binge ethanol exposure on neurodegeneration and cognitive function. Rats were given ethanol three times daily for 4 days. Silver staining revealed neurodegeneration in the olfactory bulb, piriform cortex, perirhinal cortex, entorhinal cortex, and dentate gyrus. After withdrawal, behavioral testing in the Morris water maze revealed significant differences in reversal learning between treatment groups. Ethanol-treated animals required more trials to learn the reversal task, entered the previously trained quadrant more often, and spent more time there than controls. [3H]PK-11195 binding, an index of CNS damage, was elevated in the piriform cortex of ethanol-treated animals. Thus, binge ethanol exposure resulted in neurodegeneration of a corticolimbic circuit with common excitatory inputs from the olfactory bulb and was associated with perseverative responding on a spatial learning task. These studies suggest that a single binge drinking episode could cause neurodegeneration and cognitive dysfunction in humans. The perseverative nature of the behavioral deficit could be related to both cognitive dysfunction and the behavioral components of the addiction process.

Animals↗