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Drug Alcohol Depend. 2011 Nov 1;118(2-3):288-94. doi: 10.1016/j.drugalcdep.2011.04.007. Epub 2011 May 5.

Application of the conditioned taste aversion paradigm to assess discriminative stimulus properties of psychostimulants in rats.

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Drug Safety Research Laboratories, Takeda Pharmaceutical Company Limited, 17-85, Jusohonmachi 2-chome, Yodogawa-ku, Osaka 532-8686, Japan.



The conditioned taste aversion (CTA) paradigm is one of the reliable methods to evaluate the discriminative stimulus properties of drugs and is characterized by a short conditioning period and no need for special equipment. This method, however, has not yet been fully investigated for psychostimulants such as cocaine and methamphetamine.


In the present study, rats were trained to discriminate between cocaine and a vehicle using CTA and substitution tests with various psychostimulants were conducted to evaluate the usefulness of the method for assessing the discriminative stimulus properties of this pharmacological class. Male rats received an intraperitoneal (i.p.) injection of cocaine (10mg/kg) 10 min prior to access saccharin for 20-min, and immediately after the saccharin access they received an i.p. dose of LiCl (1.8 mEq; n=8, Group CL) or the vehicle (n=8, Group CW) on the day of conditioning; on the other days (2 or 3 days between the cocaine conditioning days), they were injected with saline prior to access to saccharin without the LiCl or vehicle injection after the access.


By the fifteenth cocaine conditioning trial, all animals acquired discrimination. In the substitution test, cocaine dose dependently decreased saccharin consumption. The psychostimulants, methamphetamine, methylphenidate, bupropion and sibutramine, substituted for cocaine, whereas the opioid μ agonist morphine and the cannabinoid agonist, Δ9-tetrahydrocannabinol, did not substitute for cocaine. Mazindol did not substitute for cocaine although it has CNS stimulant activities.


These results suggest that discriminative stimulus properties of psychostimulants can be evaluated using the CTA paradigm.

[Indexed for MEDLINE]

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