Some Effects of a Hallucinogenic Compound

1226 NATURE VOL. 224 DECEMBER 20 1969

< 0·005). The M 285 group, however, shows only a very Some Effects of a Hallucinogenic slight and insignificant increase in response rate in the Compound (Cyprenorphine RCL session. Because the RC light remained on for as Hydrochloride; M 285) on the long as the lever was depressed, the longer average response duration of the saline group in the second half Light Reinforced Behaviour of Rats hour of the experimental session also shows a greater CYPRENORPHINE hydrochloride (M 285) 1 is a morphine preference for visual stimulation. antagonist with gi·eater potency (about 35 times) paren temlly and longer duration of action than nalorphine. It Table 1. AVERAGE RESPONSE FREQUENCY (RF) .4.KD DURATION (RD) IN has been surveyed for psychotomimetic effects in groups BASELINE (NL) AND RESPONSE CONTINGENT LIGHT (RCL) CONDITIONS of five to ten pre-operative patients in the USA. After an Day l (NL) Day 2 (1 h RC steady light) dose of 0·5 mg/kg about half claimed a 0·5 hour First 0·5 hour Second 0·5 hour intramuscular RF RD RF RD RE' lW "crazy feeling" or "seeing things", usually with their eyes Saline 21·0 1·32 43·2 1·73 20·3 2·62 closed, and an irrational fear. These effects were more M 285 19·8 1·24 22·1 1·31 10·9 1·73 severe after l ·O mg intramuscularly with distinct hallucina RF represents the mean nwnber of responses per 0·5 h r,criod; . respons_e durations (RD) are expressed in seconds. Rats were miected rntrnpen tions in three of ten patients (personal communication toneally with saline (n=9) or 0·3 mg/kg M 285 (n=ll) 10 mm before the from A. L.A. Boura). experimental session on day 2. The effect of tho common hallucinogenic drugs (such as LSD-25, psilocybin, mescaline) in changing the sub It thus seems that the effect of M 285 at tho dosage ject's perception of himself and his environment suggests indicated is to depress tho LR effect in the e xperimental that sensory input has in some manner been altered. The RCL situation. One interpretation of this result is that, action of LSD-25 (and possibly other hallucinogens) steady light stimulation loses its significance for the 2 3 seems • to simulate the process of conditioning and drugged animals, as hypothesized; alternatively the effect increases the significance level of stimuli to which animals of M 285 may be to depress general motor responding are exposed. This significance lovel can presumably be including lever pressing. determined by the animal's responsiveness to the stimuli, A control experiment examined the second hypothesis. and to this studies of sensory reinforcement are relevant. The procedure was the same as in the previous experi Sensory stimulation (particularly visual) can act as a ment, with two equally matched groups of nine rats. reinforcer of operant behaviour in animals•. Moreover, After either saline or M 285 (0·3 mg/kg) injections on tho different types of visual stimulation and different pre second day, however, both groups were run for 1 h in adaptation or sensory deprivation periods result in dif the dark experimental boxes with no RC light. ferential reinforcement effccts 5- 8 , presumably by changing the arousal level of the organism. In other words, the Table 2. AVEI\AGE RESPONSE FREQUENCY AND DURATION IN BASELINE (NL) significanco of tho reinforcing stimuli depends to a large A.ND CONTROL (NL) CONDITIONS on the state of the organism. extent Day 1 (NL) Day 2 (1 hour NL) We suggested therefore that drugs with hallucinogenic 0·5 hour First 0·5 hour Second 0·5 hour effects also alter the state of the organism, resulting in a Saline 28·0 1 ·07 16·5 l ·58 5·2 1 ·61 measurable change in the significance of response con M 285 28·6 1·67 21·7 1·37 7·8 1·84 More specifically, it would be hypo Rats were injected intraperitoneally with saline (n= O) or 0·3 mg/kg ll1 285 tingent stimulation. (n = 9) 10 min before the control session on day 2. thesized that hallucinogens raise the arousal level in an that is relatively deprived visually, so that it animal Table 2 shows a typical drop-off in response rate for needs very little further stimulation. Reduced response both groups in the experimental session with no RC rates would thus be predicted for response contingent stimulation. The M 285 group, however, responded (RC) visual stimulation after drug administration. more than the saline group. hooded female rats, between 80 and 90 days slightly Thirty-six The results of this experiment provide no evidence for old, were raised and kept in normal laboratory conditions the notion that M 285 inhibits general motor responding. and illumination, with free access to food and water. It thus seems likely that the main effect is in relation to chamber was a sound-insulated, light The experimental the relative significance of the stimulation to the animal. Skinner box, 10 x 10 x 10 inches, lined on three proof Similar experiments with M 285 at 0·03 and 0·06 mg/kg walls with black Perspex. The end wall had a white failed to reveal any significant effect on light reinforced P erspex screen just above a single lever, which was about response rates. When higher dose levels were used (l·O above the metal grid floor of the box. Six of 3 inches mg/kg), response rates were depressed in both RCL and were used simultaneously. The screen could these boxes control (NL) conditions, indicating general depression of be evenly illuminated from behind, at a level (about l ·5 motor activity. at a point 3 inches above the lever and 3 foot-candles We thank Reckitt and Sons, Ltd, Hull, for supplies the screen) matched for each box and stimulus inches from of M 285, and Dr A. L. A. Boura for advice and assistance. eondition. When light was dependent on response, it The work was supported by a grant from the Medical remained for as long as the lever was depressed. Research Council. Each rat was placed in a dark experimental box for a response (lever press) produced 30 min, during which G.LOWE no change in the stimulus condition-no light (NL). Two D. I. VVILLIAMS groups of nine rats were matched on the basis of average response rate during this base-line period. On the follow Department of Psychology, ing day, one group received 0·3 mg/kg of M 285 intra University of Hull. in 0-9 per cent saline solution. The other peritoneally Received August 14; revised September 25, 1969. group was injected with saline. Ten minutes after injec tion the rats were placed in the dark experimental boxes 1 Bentley, K. W., Roura, A. L. A., Fitzgerald, A . R, Hardy, D . G.. for 1 h, with response-contingent st.eady light available. McCoubrey, A., Aikman, 111. L., and Lister, R. E., Nature ,206, 102 (l!l05). 'Bradlev, P. B., in Animal Behmriottr and Druo Action, 119 (Ciba Sym Response duration and frequency scores were recorded posium; Churchill, London, 19(14). after each period of 30 min. • Bradley, P. B., and Key, n. J., EEG Clin. Nettrophysiol., 10, 97 (1958). The results are shown in Table 1. It can be seen that • Kish, G. B., Operant Belmviour (edit. by Honig, W. I{.), 109 (Appleton, the saline group shows a typical light reinforcement (LR) Century, Crofts, New York, 1966). of RC 'Lowe, G., and Williams, D. L, Ani,n. Behav., 16,338 (1968). effect, with response rate in the first half hour • Lowe, G., an