Matching Items (2)
Filtering by
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
The epidemic of drug addiction continues to grow at an alarming rate and cocaine-related overdoses have increased by more than 33% over the last decade. Cocaine targets the mesolimbic reward system in the brain to produce the “high” felt when taking cocaine. There is currently no single cure for psychostimulant abuse, but researchers continue to find viable therapeutic options. Dopamine receptors have been a recent target for researchers. We tested a novel D3R-antagonist, SWR-5, with 905-fold D3/D2 selectivity, on addiction using a rat self- administration model and hypothesized that it would reduce motivation for cocaine. SWR-5 significantly reduced cocaine intake on a high-effort PR schedule at a dose of 10 mg/kg but did not affect sucrose intake. Also, SWR-5 did not affect either spontaneous or cocaine-induced locomotion. From our results, we concluded that SWR-5 affects motivation for cocaine, not sucrose, and does not produce adverse locomotor effects. Further research would include taking a behavioral economics approach to determine the cost/benefit ratio of taking the drug, as well as performing cue reinstatement tests to solidify whether SWR-5 plays a role in cocaine-seeking behavior.
ContributorsMokbel, Ayleen Marie Halim (Co-author) / Neisewander, Janet (Thesis director) / Sanabria, Federico (Committee member) / Vannan, Annika (Committee member) / School of International Letters and Cultures (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05