Effects of a marihuana homologue (Pyrahexyl) on avoidance learning in the gerbil.

Abstract

Pyrahexyl (synhexyl, 3-hexy1-7,8,9,10-tetrahydro-6,6,9-trimethy1-6H-dibenzo[b,d] pyran-l-ol) is a synthetic cannabis compound having behavioural effects similar to tetrahydrocannabinol (mc) one of the active principles of Cannabis sativa L (Hollister, Richards & Gillespie, 1968). Although pyrahexyl has been studied in man (Stockings, 1947; Parker & Wrigley, 1950; Thompson & Procter, 1953; Hollister & others, 1968), little is known of its specific behavioural effects except that it seems to have euphoriant properties. Recently, Abel (1969) found in rats that pyrahexyl markedly reduced the amount of time required to resume lever pressing for water after this activity had been suppressed by a fear-producing stimulus and Abel & Schiff (1969) reported that pyrahexyl increased curiosity in rats as measured by the time they spent observing other animals. We now report its effect in an avoidance learning situation. The particular testing procedure chosen assessed the effect of pyrahexyl on the acquisition of new behaviour rather than its effect upon a previously learned response as examined by Abel (1969). Six adult male Mongolian gerbils (Meriones Unguiculatus), 80-90 g, were injected intraperitoneally with 0.2 ml of a solution of pyrahexyl (2.3 mg/kg) in olive oil ; six control animals received only oil injections. After 2 h animals were placed individually into a standard two-compartment automated shuttle box (Lehigh Valley Electronics, Model 146-04) in which they could avoid being shocked through the grid floor by jumping over a barrier dividing the apparatus. An auditory signal was the conditioned stimulus and a 0.8 mA constant current electric shock the unconditioned stimulus. The conditioned stimulus preceded the onset of shock by 5 s. If an avoidance response was not made during this period, shock came on and remained on until the animal jumped over the barrier. Each presentation of the conditioned stimulus and the performance of a jumping response constituted a single trial ; 50 such trials were given each day with a 25 s interval between trials. A total of 250 trials was given over a 5-day test period. The test apparatus and recording equipment were completely automated and the animals were not disturbed once the daily test period had begun. Records were kept of the number of successful trials; the time taken to jump the barrier after each conditioned stimulus onset (jump latency); and the number of between trial jumps which were not associated with the conditioned stimulus. As shown in Fig. IA, pyrahexyl-injected animals made more avoidance responses on the first day of testing than did control animals ; this difference was statistically significant (t-test, Edwards, 1964; t = 1.89, P<0.05). By the second test day all animals had achieved high performance levels and no differences in acquisition of the avoidance response were found between groups on this or any subsequent day. However, analysis of variance (Edwards, 1964) showed that, compared to controls pyrahexyl-injected animals had significantly lower response latencies to the conditioned stimulus throughout the five day test period (F = 11, 21, df, 1, 10, P<0.01, see Fig. 1B). There was no effect of the drug on responding independent of presentation of the conditioned stimulus (between-trial jumps). The mean daily between-trial jump rates were : pyrahexyl animals, 5C = 12.19, range 2.8-47; control animals, X = 14.32, range 4-0-50.