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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 …

Discriminative Stimulus Effects Of Putative Antipsychotic Drugs, Alex Lekander

All NMU Master's Theses

This study attempted to further explore the discriminative stimulus properties of antipsychotic drugs, by establishing the typical antipsychotic drug chlorpromazine, and the atypical antipsychotic drug clozapine as discriminative stimulus in two different groups of rats. The rats trained to discriminate chlorpromazine from vehicle failed to do so reliably, however nine of ten rats trained to discriminate 1.25 mg/kg clozapine from vehicle were able to acquire the discrimination in 19.1 sessions. The clozapine cue partially generalized (63.13% drug lever responding [SEM = ± 18.91]) to the antimalarial drug methylene blue at the 7.5 mg/kg dose, but not to the antimalarial quinacrine. …

Discriminative Stimulus Effects Of Gabapentin, Michael Zuidema

All NMU Master's Theses

The present study sought to evaluate the discriminative stimulus effects of the anticonvulsant gabapentin in rats trained to discriminate 30.0 mg/kg gabapentin from vehicle in a two-lever drug discrimination task. All of the ten rats tested were able to establish gabapentin as an interoceptive cue. Gabapentin produced full generalization (≥ 80% gabapentin-lever responding) for itself at 30.0, 60.0, and 120.0 mg/kg doses. Pentobarbital produced full substitution, while pregabalin, carbamazepine, fentanyl, and buspirone produced partial substitution (≥ 60% gabapentin-lever responding) for gabapentin. Ethanol and raclopride did not substitute for gabapentin. The psychostimulant amphetamine did not produce substitution; however, the 0.25 mg/kg …

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 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 …

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, …

Discriminative Stimulus Properties Of 3-Substituent Rimonabant Analogs, D. Matthew Walentiny

Theses and Dissertations

Cannabinoid agonists (e.g., THC) dose-dependently decrease locomotor activity and body temperature and produce antinociception and catalepsy. Drugs that produce this tetrad of effects within a limited dose range are likely to function as CB1 receptor agonists. A structure activity relationship study from our laboratory investigating analogs of the CB1 antagonist rimonabant revealed that certain alterations in the 3-substituent of rimonabant’s pyrazole core conferred agonist-like properties in the tetrad. Interestingly, these effects were present in CB1 -/- mice, and were not reversed by rimonabant in wild-type mice. The present study evaluated two novel 3-substituent rimonabant analogs, O-6629 and O-6658 in the …

Examination Of The Discriminative Stimulus And Cross-Tolerance Inducing Properties Of N-Desmethylclozapine In C57bl/6 Mice., Jason Wiebelhaus

Theses and Dissertations

Due to its unique receptor binding profile and its relationship to clozapine, N-desmethylclozapine (NDMC) has been examined as a possible antipsychotic drug (APD). Clozapine has been trained as discriminative stimulus in our lab, but NDMC has not yet been established as a discriminative stimulus. In experiment 1, 12 C57BL/6 mice were trained to discriminate 10.0 mg/kg NDMC from VEH using a standard-two lever operant procedure to assess antipsychotic substitution. The typical APD clozapine fully substituted for NDMC at 2 doses tested (2.5 and 5.0 mg/kg), while typical APD haloperidol failed to substitute for NDMC. In Experiment 2, 11 mice were …