Matching Items (5)
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- All Subjects: self-administration
- Creators: Neisewander, Janet
Description
Research suggests that the more positive the first drug experience, the more likely addiction will develop. Since smoking is initiated in a social setting, it is surprising how little is known about social context effects on acquisition of nicotine self-administration. We investigated this issue in rats during late adolescence using conjoined self-administration chambers that had a removable shared wall. Rats were assigned to training conditions with either a solid black plexiglass or wire mesh partition in place throughout 22 subsequent 2-hour daily training sessions. Initially, 58 day-old (late-adolescent) male and female rats received 2, 30-min habituation sessions/day over 2 consecutive days, with only an inactive lever present. Sessions began with presentation of a retractable lever and thereafter each response on that lever resulted in simultaneous delivery of saline or 1 of 2 doses of nicotine (0.015 or 0.030 mg/kg, IV) and lever retraction for a 20-second time out. The findings indicate that the social context inhibits nicotine self-administration in female rats during the development of addiction, but has little effect on the initial stages of drug acquisition. Furthermore, the data suggest that in male rats the social context enhances responding independent of nicotine, but has few effects on nicotine self-administration during the development of addiction. The findings have important implications for substance use disorders.
ContributorsDufwenberg, Martin (Author) / Neisewander, Janet (Thesis director) / Deviche, Pierre (Committee member) / Peartree, Natalie (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / School of Politics and Global Studies (Contributor) / School of Life Sciences (Contributor)
Created2015-05
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
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
Approximately five million Americans suffer from cocaine use disorder with no FDA approved pharmaceutical to help their path to recovery (Yerby, 2019). Serotonin is heavily implicated in cocaine use and in the reward system, and is therefore a suggested target for pharmaceuticals aiming to aid in psychostimulant addiction (Sarlin, 2019; Clark and Neumaier, 2001). CP 94,253, a 5-HT1BR agonist, has been shown to increase cocaine intake during maintenance of daily cocaine self-administration, though it has also been shown to decrease intake after a period of forced abstinence (Parsons et al., 1998; Pentowski et al., 2009). While a decrease in cocaine intake post-abstinence is promising post-abstinence, it remains to be seen whether this is a viable option if patients relapse. Most experiments are conducted with male rats, though an increasing amount of data has come to light on the differing effects of drugs on male and female rats (Mennenga and Bimonte-Nelson, 2014). Previous studies conducted through our lab have shown no difference in cocaine self-administration behavior across the estrous cycle phases with CP 94,253. It remains to be seen however, whether CP 94,253 would function dissimilarly in female rats than in male rats. This experiment studied the effects of CP 94,253 on post-abstinence and post-resumption cocaine self-administration in free-cycling female rats across two doses of cocaine. It was shown that CP 94,253 reduces cocaine intake both post-abstinence and post-resumption, suggesting that this pharmacotherapy would work in cases of relapse, and that there are no sex differences in its effects. While more studies should be conducted with locomotion and stress tests, thus far this experiment provides further evidence for the validity of CP 94,253 to be a promising pharmacotherapeutic option for future investigation.
ContributorsDoyle, Sophia Marie (Author) / Neisewander, Janet (Thesis director) / Olive, Foster (Committee member) / Scott, Samantha (Committee member) / School of Life Sciences (Contributor) / School of International Letters and Cultures (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05