Matching Items (3)
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- All Subjects: Cocaine
- All Subjects: Calcium
- Creators: Gipson-Reichardt, Cassandra
Description
Cocaine is a powerful psychomotor stimulant that can affect serotonin (5HT), dopamine, and norepinephrine systems in the brain. Previous studies with 5HT1B receptor agonist, CP94253, have shown dose-dependent decreases in cocaine-self administration in male rats during maintenance. However, these studies do not take into consideration sex differences between male rats and female rats. Female rats introduce a new complexity because they constantly undergo an estrous cycle that consists of four phases, metestrus, diestrus, proestrus, and estrus. It was hypothesized that cocaine infusions and active lever response rates would greatly decrease during proestrus and estrus in comparison to metestrus and diestrus due to hormonal level differences of LH, FSH, progesterone, and estradiol. In this study, female rats were trained to self-administer a training dose of 0.75 mg/kg/infusion on a fixed progressive ratio (FR5). Rats were then pretreated with CP94253 to test the effects of this 5HT1B agonist on female rat cocaine self-administration during the estrous cycle. Results showed there was no three-way interaction between cycle phase, pretreatment, and cocaine dose on infusions or active lever responses. However, pretreatment with CP94253 decreased cocaine intake and active lever responses at high cocaine doses, regardless of cycle phase. Lastly, there was a two-way interaction between pretreatment and cycle phase in which active lever responses decreased during diestrus and proestrus. These results imply that CP94253 enhances cocaine's effect regardless of cycle phase. Future work can work with ovariectomized (OVX) female rats to observe cocaine self-administration during controlled cycle phases.
ContributorsNguyen, Toan Thai Tran (Author) / Neisewander, Janet (Thesis director) / Gipson-Reichardt, Cassandra (Committee member) / Scott, Samantha (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
The serotonin (5-hydroxytryptamine, 5-HT) system is implicated in the study of drug addiction. Of the 14 known serotonin receptor subtypes, the 5-HT7R is the most recently discovered and, therefore, one of the least rigorously studied. However, the 5-HT7R has been shown to play a role in multiple psychiatric conditions, including depression, anxiety, and alcoholism. This is not surprising, as the 5-HT7R is expressed in brain regions associated with emotion and reward, such as the amygdala, dorsal raphe nucleus, and striatum. MC-RG19 is a novel 5-HT7R antagonist which has >114-fold selectivity for the 5-HT7 over other serotonin receptors. This compound was developed by our collaborators at the Temple University School of Pharmacy. Due to this specificity, and the implications of the 5-HT7 in behavior, we hypothesized that MC-RG19 would have an effect on addiction-related behaviors. We investigated the effects of MC-RG19 on spontaneous locomotion, cue-induced reinstatement, and cocaine/sucrose multiple schedule self-administration. We observed a dose-dependent decrease in spontaneous locomotor activity with significance at a MC-RG19 dose of 10 mg/kg. A dose of 5.6 mg/kg, which did not significantly decrease locomotion, significantly reduces cocaine-seeking behavior (active lever pressing) in response to the reintroduction of drug-paired cues after a period of extinction. No dose (3, 5.6, or 10 mg/kg) produced a significant effect on a multiple schedule of self-administration with alternating availability of sucrose and cocaine as the reinforcer. These results indicate that MC-RG19 has an effect on the incentive \u2014 motivational properties of reward-paired cues.
ContributorsCarlson, Andrew Kenneth (Author) / Neisewander, Janet (Thesis director) / Gipson-Reichardt, Cassandra (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Adolescent mental health problems are predicative of future problems such as depression, anxiety, ADHD, compulsive disorder, and substance use. Previous studies show that in emerging adulthood, the high prevalence and associated burdens of psychopathology increase vulnerability to disorders. These diagnoses are less common but are more severe and chronic (Tanner et al., 2009). The causes of these disorders are still being explored with recent studies showing that these mental health problems are genetically influenced. This makes understanding which gene that corresponds to what biological system is important in determining mental health. From recent studies, genes that code for calcium channels are good candidates for mental health problems. These voltage-gated channels are important mediators for physiological functions in the central nervous system and their activation provides unique responses within the brain. In a previous study, it supports the association of polymorphisms in calcium and potassium channels with the genetic risk for bipolar disorders and other mental illness (Imbrici et al., 2013). The purpose of the study was to examine if calcium channel genes influence childhood psychiatric symptoms. The first goal of this study was to form a polygenic risk score representing genetic influence on calcium channels. The second goal was to use this risk score in genetic association analyses to understand genetic risk for childhood psychopathology. Overall, the study did accomplish the goal as a polygenic risk score was created and was used to examine genetic association with child psychopathology. Based on the results, the polygenic risk score was not correlated with either parent or child- reported symptoms; however, results did show that disorders were related to each other and differed by race.
ContributorsTang, Derek (Author) / Lemery, Kathryn (Thesis director) / Gipson-Reichardt, Cassandra (Committee member) / Elam, Kit (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05