The present investigation sought to determine whether drugs which produce markedly different perceptual effects in man, barbital and mescaline or LSD produce different stimuli in rats. In a standard 2 lever operant test chamber, rats received sweetened milk for correct responses according to a variable interval schedule. All sessions were preceded by 1 of 2 treatments; following Treatment A, only responses on Lever A were reinforced and, in a similar fashion, Lever B was correct following Treatment B. No responses were reinforced during the first 5 min of a daily 30 min session. It was found that barbital can serve as a discriminative stimulus when this drug is paired with saline. Previously, we had demonstrated that mescaline or LSD can serve as discriminative stimuli. When barbital was administered to animals trained to discriminate mescaline or LSD and saline, they made either random responses or responses appropriate to saline treatment. This observation suggests that the stimulus properties of barbital are difference from those of the hallucinogens. A subsequent demonstration of discriminated responding when barbital and mescaline or LSD were paired as discriminative stimuli supports this conclusion. The present results extend previous findings which suggest that the degree of similarity or difference of drug stimuli in rats is congruent with the degree of similarity or difference of perceptual drug effects in man.

Animals↗

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A sensitive method for determining levels of [-]-2,5,-dimethoxy-4-methylamphetamine in the brain tissue.

INTRODUCTION: Indolamine and phenethylamine hallucinogens are drugs of abuse and, as well, mimic some aspects of idiopathic psychosis. To assist in investigating the mechanisms of action of (-)2,5-dimethoxy4-methylamphetamine ([-]-DOM), a member of the phenethylamine class of serotonergic hallucinogens, a sensitive and precise method for determining its levels in the brain tissue is required. METHODS: We now describe a method for determining nanogram quantities of [-]-DOM in the rat brain tissue using D-amphetamine as an intemal standard. The method employs solvent extraction with toluene and derivatization with trifluoroacetic acid anhydride (TFAA) followed by analysis using gas chromatography-mass spectrometry (GS-MS) in the selective ion monitoring (SIM) mode. RESULTS: With SIM detection, our overall recoveries were greater than 90%. The method was reliable in terms of within-day and between-day precision, accuracy, and linearity. The procedure was applied to animal subjects to determine the in vivo [-]-DOM brain levels following intraperitoneal (ip) administration. Our findings indicate that peak levels of [-]-DOM do not coincide with the 75-min pretreatment time established by drug-induced stimulus control. DISCUSSION: This study demonstrates a sensitive and precise analytical method for the determination of [-]-DOM levels in the rat brain following systemic administration of behaviorally relevant doses.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗

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Adult↗