PubMed · 7293853
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G Calhoun, J Bolton. 1981. Hyperactivity and hyperkinesis: another perspective.. https://pubmed.ncbi.nlm.nih.gov/7293853/
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Midazolam, amphetamine, and flesinoxan were used in four rat experiments to examine the usefulness of a latent Pavlovian discrimination procedure to assess the discriminative-stimulus, or occasion-setting, properties of drugs. Experiment 1 first assessed the unconditioned effect of each of the drugs on the dependent measure used, which was immobility. Relative to saline, midazolam enhanced immobility, whereas flesinoxan, and especially amphetamine decreased it. In each of the Experiments 2-4, subjects received a limited number of training sessions during which they consistently received a footshock in a distinctive box after a drug but not after saline, or vice versa. Subsequently, non-reinforced test sessions were performed in the drug and saline states in both the conditioning box and a novel box. Relative to the saline state, rats previously shocked under midazolam were less mobile in the conditioning box under midazolam, whereas rats previously not shocked under amphetamine or flesinoxan were more mobile under the drug. The remaining animals did not show differential responding. The response profiles were accounted for in terms of the combined operation of an associative, or occasion-setting, effect and a non-associative effect of the drug-induced states.
Fourteen different metabolic precursors of amphetamine or methamphetamine have previously been identified. Many of these drugs are available only by prescription and several are only available in some parts of the world and not in others. One of these drugs, famprofazone, is available over-the-counter which complicates the interpretation of methamphetamine urine drug testing results. To assist in the interpretation of typical laboratory results, a study was conducted to determine the enantiomeric composition of the methamphetamine and amphetamine produced from the metabolism of famprofazone. Fifty mg of famprofazone was administered to a volunteer followed by collection of urine for the next 6 days. The resulting quantity, enantiomeric composition and percent conversion from famprofazone to the product amphetamine and methamphetamine was determined. The results showed the amphetamine and methamphetamine to include both the d- and l-enantiomers. Percent conversion and peak concentrations were similar to those reported in previous studies.
Acute administration of the 5-HT2C/2B receptor agonist 1-(3-chlorophenyl)piperazine (mCPP, 5-10 mg/kg i.p.) induced hyperglycemia in rats. These changes were diminished in a dose-dependent manner by the 5-HT1/5-HT2 receptor antagonist methysergide and the 5-HT2A/2B/2C receptor antagonist ritanserin. In addition, mCPP-induced hyperglycemia was dose dependently diminished by the ganglionic blocker hexamethonium and was prevented by prior adrenodemedullation. Neither the 5-HT2A receptor antagonist ketanserin nor the 5-HT3/5-HT4 receptor antagonist (3-alpha-tropanyl)-1 H-indole-3-carboxylic acid ester (ICS 205-930) proved effective against mCPP-induced hyperglycemia. Lastly, administration of the 5-HT2A/2C receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)2-aminopropane (DOI) increased plasma glucose levels through ketanserin- and ritanserin-sensitive processes. Our results suggest that hyperglycemia elicited by mCPP is mediated by 5-HT2C and/or 2B receptors, and in turn adrenomedullary catecholamine release, whereas that elicited by DOI involves 5-HT2A receptors.