Discriminative stimulus properties of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane [(+/-)DOI] in C57BL/6J mice.
Randy L Smith, Robert J. Barrett, Elaine Sanders‐bush
Psychopharmacology February 2003 DOI: 10.1007/s00213-002-1252-6 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study Peer reviewed |
|---|---|
| Population | C57BL/6J mice |
| Interventions | DOI MDL 100 907 SB 206 553 SB 242 084 |
| Dose | DOI 2.5 mg/kg; MDL 100,907 0.25 mg/kg; SB 206,553 and SB 242,084 doses not specified; DOI 5.0 mg/kg for surmountability test |
| Measures | drug discrimination (percent drug lever responding) |
| Key findings | In mice, DOI's discriminative stimulus effects were dose-dependent and blocked by the 5-HT2A antagonist MDL 100,907, while 5-HT2C antagonists also attenuated them, indicating a small but significant role for 5-HT2C receptors in addition to the prominent 5-HT2A role. |
Abstract
The drug discrimination procedure has proven to be a valuable tool for studying the mechanism of action of psychoactive drugs. Recently, mice with targeted gene mutations have been developed that may also prove useful in evaluating the role of specific receptors in mediating the actions of drugs. We were interested in studying the effects of hallucinogens in genetically modified mice using the drug discrimination procedure. To establish the training procedures and characterize the stimulus properties of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane [(+/-)DOI] versus saline in wild-type mice. Using a two-lever drug discrimination procedure, C57BL/6J mice were trained to discriminate (+/-)DOI (2.5 mg/kg) from saline on a VI 30-s schedule of reinforcement. The acquisition function was orderly and similar to that found previously with rats, although the training dose required for the mice was four times higher (2.5 versus 0.75 mg/kg). The dose-response relationship indicated that percent drug lever responding was dose-dependent. Two other hallucinogens, LSD and (-)DOB, substituted fully for (+/-)DOI. Mice were tested for their ability to discriminate (+/-)DOI following pretreatment with the 5-HT(2A) receptor antagonist MDL 100,907, or with 5-HT(2C) selective antagonists, SB 206,553 or SB 242,084. A dose of 0.25 mg/kg MDL 100,907 essentially completely blocked the discriminative stimulus effects of 2.5 mg/kg (+/-)DOI. Surprisingly, both SB 206,553 and SB 242,084 also attenuated the effect of 2.5 mg/kg (+/-)DOI. The effect of SB 206,553 was surmountable at 5.0 mg/kg (+/-)DOI. These data agree with the results from studies with rats indicating a prominent role for the 5-HT(2A) receptors in mediating the discriminative stimulus effects of (+/-)DOI but in addition, suggest a small but significant role for the 5-HT(2C) receptor in mice.