Matching Items (8)
Description
Variability in subjective response to alcohol has been shown to predict drinking behavior as well as the development of alcohol use disorders. The current study examined the extent to which individual differences in alcohol pharmacokinetics impact subjective response and drinking behavior during a single session alcohol administration paradigm. Participants (N = 98) completed measures of subjective response at two time points following alcohol consumption. Pharmacokinetic properties (rate of absorption and metabolism) were inferred using multiple BAC readings to calculate the area under the curve during the ascending limb for absorption and descending limb for metabolism. Following the completion of the subjective response measures, an ad-libitum taste rating task was implemented in which participants were permitted to consume additional alcoholic beverages. The amount consumed during the taste rating task served as the primary outcome variable. Results of the study indicated that participants who metabolized alcohol more quickly maintained a greater level of subjective stimulation as blood alcohol levels declined and reported greater reductions in subjective sedation. Although metabolism did not have a direct influence on within session alcohol consumption, a faster metabolism did relate to increased ad-libitum consumption indirectly through greater acute tolerance to sedative effects and greater maintenance of stimulant effects. Rate of absorption did not significantly predict subjective response or within session drinking. The results of the study add clarity to theories of subjective response to alcohol, and suggest that those at highest risk for alcohol problems experience a more rapid reduction in sedation following alcohol consumption while simultaneously experiencing heightened levels of stimulation. Variability in pharmacokinetics, namely how quickly one metabolizes alcohol, may be an identifiable biomarker of subjective response and may be used to infer risk for alcohol problems.
ContributorsBoyd, Stephen (Author) / Corbin, William R. (Thesis advisor) / Chassin, Laurie (Committee member) / MacKinnon, David (Committee member) / Olive, Michael Foster (Committee member) / Arizona State University (Publisher)
Created2014
Description
While the concept of healthcare is largely respected in Arab culture, the stigma underlying mental health is particularly startling. This study examined the differences in mental health treatment-seeking behaviors using data from Arabs living in Syria (12.9%) and Arabs (25.6%) and non-Arabs (61.5%) living in the United States of ages 18-60. A Web-based survey was developed to understand how factors like religiosity, acculturation, and positive attitudes towards psychological treatment increased help-seeking behaviors. This survey was also provided in Arabic to include non-English speaking participants. It was hypothesized that Arab-American individuals will be more open to pursuing professional psychological help when suffering from mental symptomology (i.e. anxiety) than individuals who identified as Syrian-Arabs. In contrast, both Syrian-Arabs and Arab-Americans would definitely pursue professional help when suffering from physical symptomology (i.e. ankle sprain). Striking differences were found based on Western acculturation. Findings suggested that Arab-Americans were less inclined towards treatment and more trusting of an in-group physician ("Dr. Ahmed") whereas Syrian-Arabs were more inclined to pursue psychological treatment and preferred to trust an out-group physician ("Dr. Smith"). The results of this study identify main concerns regarding Arab attitudes towards seeking mental health treatment, which can better inform future research and mental health services for this minority.
ContributorsRayes, Diana S (Author) / Brewer, Gene (Thesis director) / Cohen, Adam (Committee member) / Olive, Michael Foster (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor)
Created2015-05
Description
Nicotine use is an outstanding public health problem with associated social and economic consequences. Nicotine is an active alkaloid compound in tobacco and is recognized as a psychoactive drug. Preclinically, nicotine addiction and relapse can be modeled using a self-administration-reinstatement paradigm. Here, we used a nicotine self-administration and contingent cue-induced reinstatement model to examine rapid, transient synaptic plasticity (t-SP) induced by nicotine cue-triggered motivation. Although preliminary, treatment with the NMDA GluN2B subunit antagonist, ifenprodil, reduced reinstated nicotine seeking, and increased the percentage of spines with smaller head diameters. Thus, future studies are needed to fully parse out the role of NAcore GluN2B receptors in cued nicotine seeking and t-SP.
ContributorsMccallum, Joseph John (Author) / Gipson-Reichardt, Cassandra (Thesis director) / Neisewander, Janet (Committee member) / Olive, Michael Foster (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
Previously we found that the serotonin 1B receptor (5-HT1BR) agonist CP 94,253 (CP) enhances the reinforcing properties of cocaine when given to male rats self-administering the drug daily, however, CP had the opposite effect following a 21-day period of abstinence. Methamphetamine, like cocaine, has similar mechanisms of action on the monoamine neurotransmitter systems. Therefore, we predicted that CP would have effects on the reinforcing properties of methamphetamine similar to cocaine. Additionally, we examined effects of the FDA-approved 5-HT1B/DR agonist, zolmitriptan, on psychostimulant self-administration. We first tested the effects of CP on methamphetamine self-administration utilizing a fixed ratio or progressive ratio schedule of reinforcement and found that regardless of whether or not rats experienced abstinence, CP decreased methamphetamine intake. We next verified that the effects of CP were mediated by 5-HT1BRs by demonstrating they were reversed when paired with a 5-HT1BR antagonist. We then tested the effects of zolmitriptan on methamphetamine responding and found the same results as found with CP. Finally, we tested whether the effects of zolmitriptan generalize to female rats. Both male and female rats were given access to various doses of cocaine after treatment with zolmitriptan. We also ruled out 5-HT1BR ligands has having an effect on locomotion, to rule out motor impairment as the reason behind the decreases in drug intake. Unlike our previous findings with CP effects on cocaine self-administration, zolmitriptan attenuated cocaine intake both before and after abstinence in both male and female rats. The pre-abstinence effects of zolmitriptan in attenuating intake of different psychostimulants suggest its potential as a pharmacological treatment for psychostimulant use disorders.
ContributorsCotter, Austin Richard (Author) / Neisewander, Janet (Thesis director) / Newbern, Jason (Committee member) / Garcia, Raul (Committee member) / School of International Letters and Cultures (Contributor) / School of Life Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Substance abuse costs the United States over $740 billion annually in healthcare, law enforcement, rehabilitation, and decreased work productivity costs. While there are certain clinical treatments for nicotine, opioid, and alcohol addiction, there is yet an equivalent treatment for psychostimulant addiction. The 5-HT7 receptor (5-HT7R) is one of the more recently discovered members of the serotonin receptor family. The involvement of 5-HT7Rs in thermoregulation, memory, and circadian rhythms, suggests that the receptor also plays a role in mood regulation, making it a potential target in the treatment of psychiatric disorders. Given’ the distribution of the 5-HT7Rs in the brain and its known cellular functions, the receptor has also been implicated in addiction processes. Most studies to date have mainly focused on psychiatric conditions like depression, having yet to explore the role of 5-HT7Rs in psycho-stimulant behaviors. In our study, the effects of SB 269970(SB), a selective antagonist for 5-HT7Rs, were tested on 8-OH-DPAT induced hypothermia, cocaine-induced locomotion, and fos expression in the nucleus accumbens. We found that SB effectively reversed 8-OH-DPAT induced hypothermia, indicating the drug is indeed binding to the 5-HT7R. However, while cocaine did increase locomotor activity and fos expression in the nucleus accumbens in rats, SB had no effect on either measure. These results suggest that 5-HT7Rs may work through pathways other than motor and should be explored through additional behavioral tests. Other brain regions should also be studied for fos expression to see if there is a region-specific effect of 5-HT7Rs and fos expression. The efficacy of SB to 5-HT7Rs and results of past studies on the drug suggests its potential as a pharmacological treatment for psychostimulant disorders.
ContributorsZheng, Margaret (Author) / Neisewander, Janet (Thesis director) / Olive, Michael (Committee member) / Garcia, Raul (Committee member) / School of Life Sciences (Contributor) / School of International Letters and Cultures (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Cocaine use remains a prevalent problem, yet there are no effective pharmacological treatments against cocaine use disorders. Cocaine is known to affect serotonin neurotransmission in the brain. Previous data has shown the modulatory role of CP 94,253, a serotonin 1B receptor (5-HT1BR) agonist on cocaine self-administration at different periods of the use-abstinence-relapse cycle. CP 94,253 facilitates cocaine self-administration in rats during the use maintenance phase, where rats are receiving daily intake of cocaine, yet attenuates it after a period of abstinence, when drug delivery is discontinued and rats are placed in home cages. Here we study the therapeutic potential of 5-HT1BR agonist pre-treatment on cocaine self-administration during these different time periods. Male and free-cycling female rats were trained to lever-press for cocaine (0.75 mg/kg i.v.) or sucrose pellets, until they met stable performance for total number of infusions on a fixed ratio 5 schedule of reinforcement. Rats were then tested with either the FDA-approved but less selective 5-HT1BR agonist zolmitriptan (3, 5.6, and 10 mg/kg s.c.; in descending order) prior to a period of abstinence or the more selective 5-HT1BR agonist CP 94,253 (5.6 mg/kg s.c.) after a period of prolonged abstinence and relapse (i.e. resumption of daily cocaine self-administration after a period of abstinence). Each session ran for 2 hours during which the training dose was available for the 1st hour and a low dose of cocaine (0.075 mg/kg i.v.) for the 2nd hour. Zolmitriptan was found to attenuate cocaine self-administration measures at a dose of 3 and 5.6 mg/kg when testing at the low dose of cocaine and at all three doses (3, 5.6, and 10 mg/kg) when testing at the training dose of cocaine. Zolmitriptan at the doses effective at attenuating cocaine intake did not alter sucrose self-administration. CP 94,253 (5.6 mg/kg s.c.) was found to have significant attenuative effects on self-administration measures both after a period of prolonged abstinence and after a period of relapse. Overall, these experiments showed that zolmitriptan decreased cocaine reinforcement without altering sucrose reinforcement as well as that CP 94,253 attenuates cocaine intake even after a period of relapse. These findings support the therapeutic potential of 5-HT1BR agonists as pharmacological treatments for cocaine use disorders.
ContributorsLe, Tien (Author) / Neisewander, Janet (Thesis director) / Newbern, Jason (Committee member) / Garcia, Raul (Committee member) / Chemical Engineering Program (Contributor, Contributor) / School of International Letters and Cultures (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Serotonin 1B receptor (5-HT1BR) agonists enhance cocaine intake in rats during daily self-administration (SA) sessions, yet decrease cocaine intake after prolonged abstinence. The goal of my dissertation was to examine if 5-HT1BRs are suitable targets for treatment development to attenuate psychostimulant intake. I first investigated if 5-HT1BR agonist effects that had been observed with cocaine generalize across psychostimulants, i.e., methamphetamine. Rats trained to self-administer methamphetamine received either CP 94,253 or the clinically-available but less selective 5-HT1D/1BR agonist, zolmitriptan, prior to tests for effects on SA both before and after a 21-day abstinence period. I found that CP 94,253 and zolmitriptan decreased the reinforcing and incentive motivational effects of methamphetamine, regardless of abstinence, unlike the pre-abstinence increase in cocaine SA observed previously with 5-HT1BR agonists. The attenuating effects of CP 94,253 on methamphetamine were antagonized in a 5-HT1BR-mediated manner. Subsequently, I investigated the efficacy and mechanism involved in effects of zolmitriptan on cocaine SA in male and female rats. Rats trained to self-administer cocaine received zolmitriptan prior to tests for effects on SA before a 21-day abstinence period. I found that zolmitriptan decreased cocaine intake in both sexes regardless of abstinence and without altering sucrose intake. I further demonstrated that the zolmitriptan effects on cocaine SA were mediated by both 5-HT1BRs and 5-HT1DRs. Finally, I examined if the abstinence-induced decrease in cocaine intake observed with the selective 5-HT1BR agonist, CP 94,253, persists during relapse after abstinence or reverts to enhancing cocaine intake, similar to effects observed without an abstinence period. Rats trained to self-administer cocaine resumed daily cocaine SA sessions after the forced abstinence period to investigate the effects of CP 94,253 on cocaine relapse. I found that CP 94,253 attenuated cocaine intake in relapse tests, suggesting that the abstinence-dependent attenuation of CP 94,253 on cocaine SA remains even after resumption of daily cocaine intake. The findings suggest that 5-HT1BR agonists like CP 94,253 and zolmitriptan have clinical potential as treatments for psychostimulant use disorders.
ContributorsGarcia, Raul (Author) / Neisewander, Janet L (Thesis advisor) / Olive, Michael Foster (Committee member) / Sanabria, Federico (Committee member) / Newbern, Jason M (Committee member) / Arizona State University (Publisher)
Created2020
Description
Background: 5-HT1B receptor agonists enhance cocaine intake during daily self-administration sessions but decrease cocaine intake when tested after prolonged abstinence. We examined if 5-HT1B receptor agonists produce similar abstinence-dependent effects on methamphetamine intake.
Methods: Male rats were trained to self-administer methamphetamine (0.1 mg/kg, i.v.) on low (fixed ratio 5 and variable ratio 5) and high (progressive ratio) effort schedules of reinforcement until intake was stable. Rats were then tested for the effects of the selective 5-HT1B receptor agonist, CP 94,253 (5.6 or 10 mg/kg), or the less selective but clinically available 5-HT1B/1D receptor agonist, zolmitriptan (10 mg/kg), on methamphetamine self-administration both before and after a 21-day forced abstinence period during which the rats remained in their home cages.
Results: The inverted U-shaped, methamphetamine dose-response function for intake on the fixed ratio 5 schedule was shifted downward by CP 94,253 both before and after abstinence. The CP 94,253-induced decrease in methamphetamine intake was replicated in rats tested on a variable ratio 5 schedule, and the 5-HT1B receptor antagonist SB 224,289 (10 mg/kg) reversed this effect. CP 94,253 also attenuated methamphetamine intake on a progressive ratio schedule both pre- and postabstinence. Similarly, zolmitriptan attenuated methamphetamine intake on a variable ratio 5 schedule both pre- and postabstinence, and the latter effect was sustained after each of 2 more treatments given every 2 to 3 days prior to daily sessions.
Conclusions: Unlike the abstinence-dependent effect of 5-HT1B receptor agonists on cocaine intake reported previously, both CP 94,253 and zolmitriptan decreased methamphetamine intake regardless of abstinence. These findings suggest that 5-HT1B receptor agonists may have clinical efficacy for psychostimulant use disorders.
ContributorsGarcia, Raul (Author) / Cotter, Austin (Author) / Leslie, Kenneth (Author) / Olive, M. Foster (Author) / Neisewander, Janet (Author) / College of Liberal Arts and Sciences (Contributor)
Created2017-04-22