A proposed animal model for hallucinogens based on LSD's effects on patterns of exploration in rats

The utility of various measures of exploratory activity in rats was studied in order to develop an animal model of hallucinogens. A hole board chamber, connected by a door to a home cage, provided two test situations. Rats either were placed directly into the hole board with the door closed (forced exploration) or were placed in the home cage and, following adaptation, the door was opened (free exploration). The monitoring system provided both quantitative measures (crossovers, rearings, and hole pokes) and qualitative measures of locomotor patterns. A series of four experiments, with doses of 2-160 micrograms/kg LSD, revealed three major categories of effects, distinguishable on the basis of dose dependency, time course, or response to environmental manipulation: increased avoidance of novel and central areas, disruption of the spatial patterning of locomotion, and suppression of rearing. All three effects exhibited partial tolerance 24 hr after one injection of 30 micrograms/kg LSD and complete tolerance after five daily injections. The possibility that LSD's enhancement of neophobia in rats may be a valid analogue model of its intensification of affective reactions in humans is discussed.