Applications and Limitations of the Drug Discrimination Method for the Study Of Drug Abuse

Overton, Donald A.

doi:10.1007/978-1-4612-4812-5_16

Cited by 65 publications

(35 citation statements)

References 198 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A drug is considered to function as a discriminative stimulus if subjects can be trained to respond differentially to the presence or absence of the drug. All drugs of abuse can function as discriminative stimuli, and abuse liability of a test drug is indicated if it shares discriminative stimulus effects with a known drug of abuse (Overton, 1987;Ator and Griffiths, 2003). In addition, the discriminative stimulus effects of drugs in animals are homologous to the subjective drug effects in humans in whom discrimination is evidenced by different patterns of verbal behavior rather than by differential leverpressing behavior (Schuster and Johanson, 1988;Carter and Griffiths, 2009).…”

Section: B Preclinical Models Of Cocaine Use Disordermentioning

confidence: 99%

Serotonin 5-HT₂Receptor Interactions with Dopamine Function: Implications for Therapeutics in Cocaine Use Disorder

2014

View full text Add to dashboard Cite

Section: B Preclinical Models Of Cocaine Use Disordermentioning

confidence: 99%

Serotonin 5-HT₂Receptor Interactions with Dopamine Function: Implications for Therapeutics in Cocaine Use Disorder

2014

View full text Add to dashboard Cite

“…Studies have shown that the discriminative stimuli produced by many drugs, administered singly, exert their e¤ects as multiple cues with di¤erent components (Barry and Krimmer 1979;Overton 1987). This notion has been tested by a number of laboratories who have shown that rats can be trained to discriminate a drug mixture from its vehicle Gauvin and Holloway 1993).…”

Section: Introductionmentioning

confidence: 97%

Behavioural and neurochemical characteristics of phentermine and fenfluramine administered separately and as a mixture in rats

et al. 1997

View full text Add to dashboard Cite

Clinical case studies suggest that combined administration of the serotonergic agent fenfluramine (FEN) and the weak amphetamine-like anorexic agent phentermine (PHEN) may be useful in the treatment of alcohol and cocaine addictions. The present experiment examined the nature of the interaction between the two agonists using the drug discrimination paradigm. In vivo microdialysis served to examine the neurochemical profile of dopamine and serotonin release in the nucleus accumbens. In conscious rats, acute injections of FEN (1.0-2.0 mg/kg i.p.) or PHEN (1.0-2.0 mg/kg i.p.) selectively elevated levels of serotonin and dopamine in the nucleus accumbens, respectively. A mixture (1 mg/kg of each) increased levels of both amines by similar magnitudes to those observed with each individually. Three groups of Sprague-Dawley rats were trained to discriminate (1) FEN (1.0 mg/kg i.p.) alone, (2) PHEN (1.0 mg/kg i.p.) alone or a mixture (3) PHEN+FEN (1 mg/kg of each, i.p.) from saline under a fixed ratio (FR-10) schedule of food reinforcement. Rats acquired the mixture discrimination rapidly, while for the other groups the training dose had to be increased to 2.0 mg/kg to attain stimulus control. The individual components of the mixture at the training dose generalized partially to the mixture, and complete generalisation was observed following 3.0 mg/kg FEN or PHEN. Rats trained to discriminate the individual components showed respective cross-generalisation profiles. Generalisation to cocaine (0.3-10.0 mg/kg i.p.), amphetamine (0.1-3.0 mg/kg i.p.) and nicotine (0.1-0.8 mg/kg s.c.) was greatest in the MIX-trained rats, while partial or no generalisation was observed in rats trained to discriminate the individual compounds. From the present results, it may be concluded that the two drugs given as a mixture do not produce a novel cue. Rather, these aminergics appear to interact additively. Furthermore, the dual stimulation of the amines by the mixture may be the basis for the cueing effects of the FEN+PHEN drug mixture, and its effectiveness in treating drug addictions.

show abstract

“…The discriminative stimulus (cue) effects of drugs comprise a second major behavioral process that is thought to influence abuse liability (Haretzen and Hickey1987;Holtzman 1990;Stolerman 1992). For instance, many drugs of abuse can both maintain self-administration and function as discriminative stimuli in experimental animals (Overton 1987;Overton et al 1986). The discriminative stimulus effects of drugs may reinstate drug-seeking behavior because a history of self-administration repeatedly associates the positive reinforcing aspects of a drug with distinctive stimulus effects.…”

Section: Introductionmentioning

confidence: 99%

The discriminative stimulus properties of self-administered ethanol are mediated by GABA A and NMDA receptors in rats

et al. 2001

View full text Add to dashboard Cite

Rationale: The neurobiological systems that mediate the discriminative stimulus effects of self-administered drugs are largely unknown. The present study examined the discriminative stimulus effects of self-administered ethanol. Methods: Rats were trained to discriminate ethanol (1 g/kg, IP) from saline on a two-lever drug discrimination task with sucrose (10% w/v) reinforcement. Test sessions were conducted with ethanol (0 or 10% v/v) added to the sucrose reinforcement to determine if self-administered ethanol would interact with the discriminative stimulus effects of investigator-administered ethanol, or with the ethanol-like discriminative stimulus effects of the GABA A -positive modulator pentobarbital or the non-competitive NMDA antagonist MK-801. Results: During a saline test session, ethanol (10% v/v) was added to the sucrose reinforcement. Responding by all animals began accurately on the salineappropriate lever and then switched to the ethanol-appropriate lever after rats self-administered a mean dose of 1.2±0.14 g/kg ethanol. During cumulative self-administration trials, responding initially occurred on the saline lever and then switched to the ethanol-appropriate lever after ethanol (0.68±0.13 g/kg) was self-administered. Investigator-administered MK-801 (0.01-1.0 mg/kg, cumulative IP) and pentobarbital (0.3-10.0 mg/kg, cumulative IP) dose-dependently substituted for ethanol. When ethanol (10% v/v) was added to the sucrose reinforcer, MK-801 and pentobarbital dose-response curves were shifted significantly to the left. Conclusions: Self-administered ethanol substituted for and potentiated the stimulus effects of investigator-administered ethanol, suggesting that the discriminative stimulus effects of self-administered ethanol are similar to those produced by investigator-administered ethanol. Self-administered ethanol enhanced the ethanol-like discriminative stimulus effects of MK-801 and pentobarbital, which suggests that the discriminative stimulus effects of self-administered ethanol are mediated by NMDA and GABA A receptors.

show abstract

Applications and Limitations of the Drug Discrimination Method for the Study Of Drug Abuse

Cited by 65 publications

References 198 publications

Serotonin 5-HT₂Receptor Interactions with Dopamine Function: Implications for Therapeutics in Cocaine Use Disorder

Serotonin 5-HT₂Receptor Interactions with Dopamine Function: Implications for Therapeutics in Cocaine Use Disorder

Behavioural and neurochemical characteristics of phentermine and fenfluramine administered separately and as a mixture in rats

The discriminative stimulus properties of self-administered ethanol are mediated by GABA A and NMDA receptors in rats

Contact Info

Product

Resources

About

Applications and Limitations of the Drug Discrimination Method for the Study Of Drug Abuse

Cited by 65 publications

References 198 publications

Serotonin 5-HT2Receptor Interactions with Dopamine Function: Implications for Therapeutics in Cocaine Use Disorder

Serotonin 5-HT2Receptor Interactions with Dopamine Function: Implications for Therapeutics in Cocaine Use Disorder

Behavioural and neurochemical characteristics of phentermine and fenfluramine administered separately and as a mixture in rats

The discriminative stimulus properties of self-administered ethanol are mediated by GABA A and NMDA receptors in rats

Contact Info

Product

Resources

About

Serotonin 5-HT₂Receptor Interactions with Dopamine Function: Implications for Therapeutics in Cocaine Use Disorder

Serotonin 5-HT₂Receptor Interactions with Dopamine Function: Implications for Therapeutics in Cocaine Use Disorder