To determine the effect of the drug history of rats on their subsequent operant behaviour in the rat runway procedure, we tested the mu opioid receptor agonists morphine and remifentanil and found a carryover of previous drug/saline experience that was not found for a food reinforcer. Previous exposure to saline significantly decreased the apparent reinforcing effect of subsequently offered morphine or remifentanil, while previous experience with morphine or remifentanil significantly increased responding for saline. This carryover of a previous learning experience on subsequent operant performance in the rat runway procedure cautions that the drug history should be considered and might even invalidate subsequent findings when testing drugs of abuse or other reinforcers.
View Article and Find Full Text PDFBupropion (BUP), which in its slow-release formulation (Zyban) is used as a smoking-cessation drug, increases dopamine overflow in the nucleus accumbens and serves as a reinforcer in animal experiments, both suggesting that BUP may possess some abuse liability. The present study examined if BUP produced subjective effects indicative of abuse liability in a quasi-naturalistic setting, with caffeine (CAF) serving as a positive control. In a randomized double-blind crossover design, male smokers (n = 50) ingested two doses (interdosing interval, 6 h) of placebo (PLC), 178 mg CAF, or 150 mg slow-release BUP in their normal mid-week work environment.
View Article and Find Full Text PDFAlthough 'ecstasy' (3,4-methylenedioxymethamphetamine, MDMA) is, after marijuana, the second most prevalent illegal drug of abuse in European adolescents, animal experimental evidence of MDMA's reinforcing effect has remained scarce, particularly in the rodent model, raising questions about the robustness of MDMA's reinforcing effect under controlled laboratory conditions. In the present rat runway study, Sprague-Dawley and Long-Evans rats were given the opportunity to run for intravenous injections of saline or MDMA (1 mg/kg). MDMA significantly decreased runtimes in both rat strains.
View Article and Find Full Text PDFPsychopharmacology (Berl)
August 2003
Rationale: The nature of the relationship between the dose of a drug of abuse and its reinforcing effect has come under close scrutiny. It is currently debated if the steep ascending part of the biphasic dose-response curve typically obtained in multiple-dosing lever-press-based operant conditioning procedures represents a satiety-driven, all-or-none response or if the response is gradual and tightly adjusted to the various doses of the reinforcer.
Objectives: Dose-response relationships of drug reinforcers (remifentanil, alfentanil, morphine, cocaine) as well as a physiological reinforcer, i.
Trends Pharmacol Sci
September 2002
The EuroConference/Neurochemistry Winter Conference on Modeling Addiction, held on 6-11 April 2002 in Soelden, Austria(1) explored the question of how various experimental approaches, ranging from those at the level of molecular biology to human behavior, reflect human patterns of drug abuse and dependence and whether these various approaches constitute suitable predictive or homologous models to test novel pharmacotherapies.
View Article and Find Full Text PDFAlley running has been successfully used as an operant to demonstrate both the positive and negative reinforcing effect of intravenously administered drugs of abuse in a bona fide operant conditioning paradigm, the Ettenberg runway, in which confounding drug effects on motor performance and drug accumulation are avoided. While Ettenberg and colleagues focus on the intravenous route of drug administration, we tested the practicability of the subcutaneous route of administration in this runway paradigm in Sprague Dawley rats, using morphine as the investigated drug of abuse. We also modified the Ettenberg runway, most notably in that either food (sweetened condensed milk), no food, morphine, or saline was presented outside the runway in a separate cage.
View Article and Find Full Text PDFChromogranins are neuropeptide precursors stored in large dense core vesicles in which they are processed to smaller peptides. Although these peptides are widespread in the CNS, it is still unknown if they are behaviourally active. For example, even though secretoneurin, a 33-amino acid peptide derived from secretogranin II, was shown to induce release of dopamine from rat striatal neurons, work on the functional significance of this result is still missing.
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