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Substance abuse disorders affect 15.3 million people worldwide. The field has primarily focused on dopaminergic drugs as treatments for substance use disorders. However, recent work has demonstrated the potential of serotonergic compounds to treat substance abuse. Specifically, the serotonin 1B receptor (5-HT1BR), a Gi-coupled receptor located throughout the mesocorticolimbic dopamine

Substance abuse disorders affect 15.3 million people worldwide. The field has primarily focused on dopaminergic drugs as treatments for substance use disorders. However, recent work has demonstrated the potential of serotonergic compounds to treat substance abuse. Specifically, the serotonin 1B receptor (5-HT1BR), a Gi-coupled receptor located throughout the mesocorticolimbic dopamine system, has been implicated in the incentive motivational and rewarding effects of cocaine. Our research suggests that the stimulation of 5-HT1BRs produces different effects at various time points in the addiction cycle. During maintenance of chronic cocaine administration, 5-HT1BR stimulation has a facilitative effect on the reinforcing properties of cocaine. However 5-HT1BR stimulation exhibits inhibitory effects on reinforcement during prolonged abstinence from cocaine. The aim of this study was to examine the possibility of a switch in the functional role of 5-HT1BRs in the locomotor effects of cocaine at different time points of chronic cocaine administration in mice. We found that the 5-HT1BR agonist CP 94,253 increased locomotor activity in mice tested one day after the last chronic cocaine administration session regardless of whether the chronic treatment was cocaine or saline and regardless of challenge injection (i.e., cocaine or saline). Yet after abstinence, CP 94,253 induced a decrease in locomotor activity in mice challenged with saline and attenuated cocaine-induced locomotion relative to cocaine challenge after vehicle pretreatment. These findings suggest that a switch in the functional role of 5-HT1BR is observed at different stages of the addiction cycle and further suggest that clinical applications of drugs acting on 5-HT1BR should consider these effects.
ContributorsBrunwasser, Samuel Joshua (Author) / Neisewander, Janet (Thesis director) / Pentkowski, Nathan (Committee member) / Der-Ghazarian, Taleen (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / Department of Psychology (Contributor)
Created2014-05
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The use of synthetic cathinones or "bath salts" has risen dramatically in recent years with one of the most popular being Methylendioxypyrovalerone (MDPV). Following the temporary legislative ban on the sale and distribution of this compound , a multitude of other cathinone derivatives have been synthesized. The current study seeks

The use of synthetic cathinones or "bath salts" has risen dramatically in recent years with one of the most popular being Methylendioxypyrovalerone (MDPV). Following the temporary legislative ban on the sale and distribution of this compound , a multitude of other cathinone derivatives have been synthesized. The current study seeks to compare the abuse potential of MDPV with one of the emergent synthetic cathinones 4-methylethcathinone (4-MEC), based on their respective ability to lower current thresholds in an intracranial self-stimulation (ICSS) paradigm. Following acute administration (0.1, 0.5, 1 and 2 mg/kg i.p.) MDPV was found to significantly lower ICSS thresholds at all doses tested (F4,35=11.549, p<0.001). However, following acute administration (0.3,1,3,10,30 mg/kg i.p) 4-MEC produced no significant ICSS threshold depression (F5,135= 0.622, p = 0.684). Together these findings suggest that while MDPV may possess significant abuse potential, other synthetic cathinones such as 4-MEC may have a drastically reduced potential for abuse.
ContributorsWegner, Scott Andrew (Author) / Olive, M. Foster (Thesis director) / Presson, Clark (Committee member) / Sanabria, Federico (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / Department of Psychology (Contributor)
Created2013-05