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Preclinical Behavioral Assessments Of Mitraginyne, The Main Psychoactive Alkaloid In Kratom, Rachel Burroughs

Dissertations

Mitragyna speciosa (kratom) is a medicinal plant indigenous to Southeast Asia and Africa with a long history of use for a variety of ailments, including diarrhea, pain relief, cough suppression, and amelioration of opiate withdrawal symptoms. Despite its status as an herbal remedy, kratom is banned in some countries due to a myriad of negative health risks. Preclinical psychopharmacology studies of mitragynine (MG), the main alkaloid of kratom, indicate it has opioid-like effects at higher doses and psychostimulant-like effects at lower doses. The current study utilized three rodent behavioral paradigms to evaluate the putative psychostimulant effects of MG. The specific …

Evaluation Of Α-Pyrrolidindovalerophenone (Α-Pvp) And Its Isomers In Male And Female Sprague-Dawley Rats Trained To Discriminate Mdpv, Kaley Cargile

Masters Theses

Recreational use of synthetic cathinones, 3,4-methylenedioxypyrovalerone (MDPV) and α‐pyrrolidinovalerophenone (α‐PVP), has become increasingly popular, thus prompting characterization of their behavioral and neurochemical effects. MDPV has been studied for several years now, though there is still much unknown about α‐PVP, and its isomers. The primary objective of this study was to characterize the discriminative effects of α‐PVP and its isomers in comparison to MDPV. Male and female Sprague-Dawley rats were trained to discriminate 0.5mg/kg MDPV from saline injections under a fixed ratio 20 (FR 20) schedule of food reinforcement. Substitution tests were conducted with MDPV (0.05-0.5mg/kg), α‐PVP (0.05-0.5mg/kg), (S)-α‐PVP (0.05-1mg/kg) and …

Assessment Of Dopaminergic And Serotonergic Receptor Antagonists In Male Rats Trained To Discriminate 4-Methylmethcathinone (Mephedrone), Rachel L. Burroughs

Masters Theses

Preclinical drug discrimination studies of the synthetic cathinone, 4-methylmethcathinone (mephedrone) have demonstrated its effects are comparable to those of other popular psychostimulant drugs. Few studies have directly examined the contribution of specific neurotransmitter receptors to mephedrone’s discriminative stimulus effects. The present study investigated the role of dopamine and serotonin receptors in these effects. Eight adult male Sprague-Dawley rats were trained to discriminate 3.0 mg/kg mephedrone from saline. After dose-response curves were determined with mephedrone (0.375-3.0 mg/kg), a series of stimulus antagonism tests were conducted with dopamine antagonists (Sch 23390, haloperidol) and serotonin antagonists (WAY 100,635, MDL 100,907, pirenperone) administered as …

Sex Differences In Serotonergic And Dopaminergic Mediation Of Lsd Discrimination In Rats, Keli A. Herr

Dissertations

After decades of opposition, a resurgence of interest in the psychotherapeutic potential of LSD is gaining acceptance in the medical community. Future acceptance of LSD as a psychotherapeutic adjuvant may be predicated on knowledge about its neural mechanisms of action. Preclinical drug discrimination assay offers an invaluable model to determine the neural mechanisms underlying LSD’s interoceptive stimulus effects. Unfortunately, current preclinical literature on LSD discrimination is based on results obtained exclusively in male subjects. The present study represents the first known preclinical assessment of possible sex differences in the discriminative stimulus effects of LSD.

Adult female (n=8) and male (n=8) …

Discriminative And Reinforcing Effects Of Cocaine-Levamisole Combinations, Zachary J. Zimmermann

Dissertations

The behavioral and neurochemical effects of cocaine are well established, and it is one of the most widely abused illicit drugs. Illicit cocaine is often adulterated with levamisole, which is an anthelmintic that was withdrawn from the U. S. market in 2000. It has been hypothesized that levamisole, unlike other common adulterants which are added as simple bulking agents, has effects of its own which may be responsible for its use as an adulterant. Although these effects are speculative, the addition of levamisole to cocaine has become an increasing public health concern, as serious adverse effects (e.g., vasculitis, neutropenia) of …

Discriminative Stimulus Effects Of 3,4-Methylenedioxypyrovalerone And 4-Methylmethcathinone, Michael D. Berquist

Dissertations

Recent escalation in the popularity of recreational synthetic cathinone (“bath salts”) use has prompted numerous scientific investigations of the neurochemical and behavioral effects of 3,4-methylenedioxypyrovalerone (MDPV) and 4-methylmethcathinone (4-MMC), two of the more common chemical constituents of these illicit “bath salts”. Previous neurochemical and electrophysiological studies have revealed that MDPV functions as a blocker, and 4-MMC as a substrate, at monoamine transporters, and both produce transient increases in extracellular monoamines. In addition, previous research has demonstrated that MDPV and 4-MMC support self-administration in nonhuman experimental subjects, and their rewarding effects are observed when paired with contextual cues in nonhuman models …

Discriminative Stimulus Properties Of 3.0 Mg/Kg Mephedrone In Rats, Nathyn Thompson

Honors Theses

Consumption of a prominent synthetic cathinone known as mephedrone (4-methylmethcathinone) has become a popular alternative to club drugs such as ecstasy, cocaine, and methamphetamine within the past decade. The pharmacological mechanisms that contribute to its subjective effects have yet to be fully characterized and are thus warranted for investigation. The present study employed drug discrimination methods to train eight male Sprague-Dawley rats to discriminate injections of 3.0 mg/kg mephedrone from saline. Various doses of mephedrone, 3,4-methylenedioxypyrovalerone (MDPV), d-amphetamine (AMPH), cocaine, (+)-methamphetamine (METH), and 3,4-methylenedioxy-methamphetamine (MDMA) were investigated for their ability to substitute for the stimulus cues of the training …

Evaluation Of Modafinil In Preclinical Behavioral Assays Of Abuse Liability, Amanda J. Quisenberry

Dissertations

Modafinil is an FDA-approved drug for the treatment of narcolepsy with efficacy in the treatment of chronic fatigue syndrome, obstructive sleep apnea, and shift-work sleep disorder. Modafinil’s wake-promoting and cognitiveenhancing effects are reportedly similar to those of traditional psychostimulants, but without the side effects typically associated with these substances. Modafinil has also been investigated as an agonist replacement therapy for psychostimulant dependence, although results of clinical trials are equivocal. Few studies have examined its behavioral effects in combination with psychostimulants and the neuropharmacological actions of modafinil are not well understood. The primary aim of this study was to assess modafinil’s …

Assessment Of The Discriminative Stimulus Effects And Time Courses Of Salvinorin A And Two Synthetic Salvinorin B Derivatives, Methoxylmethyl (Mom) And Ethoxymethyl (Eom), Ethers In Rats Trained To Discriminate U69,593, Lisa M. Bell

Masters Theses

Research regarding the psychopharmacology of salvinorin A, the main psychoactive ingredient in the hallucinogenic plant Salvia divinorum, has been motivated largely by a recent increase in its recreational use and widespread media attention focused on this plant and its extracts. In addition, there is considerable evidence that drugs acting on kappa opioid receptors (KOR) may have therapeutic potential in the treatment of some neuropsychiatric conditions, including drug dependence and mood disorders. Although the neuropharmacological actions of salvinorin A are well established, only a few studies have explored the behavioral effects of this substance in comparison to the KOR agonist, …