Characteristics of tetrahydrocannabinol (THC)-produced discrimination in rats
T. U. C. Järbe, J. O. Johansson, B. G. Henriksson
Psychopharmacology January 1, 1976 DOI: 10.1007/bf00423258 via Springer Nature
Summary
Rats learned to distinguish the effects of injected THC from the no-drug state in a T-shaped maze. Discrimination was dose-dependent: animals trained with higher doses of THC learned the task faster than those trained with lower doses. Δ⁸-THC appeared somewhat less potent than Δ⁹-THC. At 10 mg/kg, Δ⁹-THC produced strong state dependency, with rats reaching criterion within the first ten sessions, similar to a group trained with pentobarbital. Higher training doses led to higher ED₅₀ values. Hashish smoke maintained drug-appropriate responding in THC-trained rats. Depleting brain catecholamines or serotonin with AMPT or PCPA did not impair Δ⁹-THC discrimination.
Study at a glance
| Characteristics | Animal experiment Peer reviewed |
|---|---|
| Population | Rats |
| Keywords | Tetrahydrocannabinols Pentobarbital Hashish smoke State dependency T-maze |
| Citations | 40 |
| Key finding | THC discrimination in rats was dose-dependent, with higher training doses producing faster acquisition and higher ED₅₀ values, and neither catecholamine nor serotonin depletion affected Δ⁹-THC discrimination. |
Abstract
Rats were trained in a T-shaped maze to discriminate the effects produced by i.p. injections of tetrahydrocannabinol (THC) and the no-drug state (state-dependency, StD). Several doses of both Δ^8-THC (range: 0.75–5.0 mg/kg) and Δ^9-THC (range: 0.75–10.0 mg/kg) were used in order to compare the number of sessions required by the animals until reaching criterion performance. An additional group of rats had to discriminate pentobarbital sodium (20.0 mg/kg) from the no-drug state. Results: THC discrimination was proportional to dose i.e., animals that had to differentiate high doses of THC from no drug acquired the T-maize task faster than animals trained with the lower doses of THC. Acquisition data further suggest that Δ^8-THC is somewhat less potent than the Δ^9-isomer. Δ^9-THC (10.0 mg/kg) produces strong StD, as defined by Overton (1971), since both this group and the barbiturate group reached the criterion within the first 10 training sessions. Time and dose testings suggest that stimulus properties of drugs vary in a quantitative way and that the calculated ED_50 values are mainly determined by the training dose used. It was found that the higher the training dose used the higher was the corresponding ED_50 value. Hashish smoke can maintain drug responding among THC-trained rats. A lowered content of brain catecholamines and/or serotonin, induced by AMPT (150 mg/kg) and PCPA (310–350 mg/kg), did not lessen Δ^9-THC (2.5 mg/kg) discrimination.