o 191/486 Z7459 S ,_, /Sandoz/'cf_'. '_._._'apomorphine/Lillycf/. mescaline /Roche/ psilocybin quipazine/Miles-Ames/influence on _reflex-dru_' 'resernin¢,' reversal test 'N-metah.' basal cf. methyltyrosine/Astra/depleted '[email protected]_t/-_' '_' conc. in brain modification by phenoxybenzamine /SK +F/ chlorpromazine methysergide haloperidol /McNeil/pimozide /Janssen/clonidine /CIBA-Geigy/mouse /XXVI/ /XXXII/ Psychopharmacology 52, No.3, Z91-97 /i977/ _on M K, Clark W G, Masuoka D T /Sepulveda, _'_'=J_geles and Irvine,Cal,,USA/ Possible Involvement of the Central Dopaminergic System in the AntiresCrpine Effect of LSD, The effects of d-LSD tartrate (Sandoz) and apmorphlne HC1 (APM, Lilly) were studied in reserpinized mice, Groups of 3-20 male Swiss mice (23-28 g) were treated with reserpine (CIBA-Geigy) 5 mg/kg i,p, and 4 hr later, the following drugs were given i,p, and motor activity measured immediately: LSD and APM 0,1-6 mg/kg; mescaline HC1 (Roche) and psilocybin 5, 50, i00 and ZOO mg/kg; brom-LSD (BOL 148, Sandoz) i and _0 mg/kg and qulpazine (IViiles)Z5 mg/kg. Other animals were pretreated with LSD - day i 2 x 3 mg/kg, day 2 3 x i mg/kg and tested on day 3, 4 hr after reserpine, with either LSD or APM t mg/kg, Other reserpinized mice were given the following drugs before administration of LSD or APM I mg/kg" dl-a-methyl-p- tyrosine-methyl ester hydrochloride (a-MT, Astra) Z50 mg/kg, 5,Shr; phenoxybenzamine (SK+F) 10 mg/kg, i hr; chlorpromazine .-IC1 (CPZ, SK+F) 3 mg/kg; methyser_ide (Sandoz) 3 mg/kg, 15 rain; haloperidol (McNeil) _ or 5 mg/kg, 15 rain; pimozide (Janssen) 0,5 or 3 mg/kg, 2 hr and clonidine (CIBA-Geigy) l mg/kg, 3 rain before. Groups of novice mice received LSD or APM 3 mg/'kg or saline and l0 rain later some received c-MT 250 mg/kgbase, All were killed 3hr later and brain catechol- amines (CA) were determined. Reserpinized mice were completely inactive in 4 hr, Both LSD and APM dose-dependently antagonized this depression within 3 mln. Brom-LSD, mescaline, psilocybin and quipazine did not produce locomotor stimulation. Tolerance did not develop to the effect of LSD nor between LSD and APM. a-MT and phenoxybenzamine did not alter the motor response to LSD or APM. Methysergide potentiated the APM. but not LSD, effect. CPZ, haloperidol and pimozide almost completely abolished the APM response and significantly reduced the LSD response, Clonidine pretreatment produced motor excitation in LSD and APM treated mice, Neither APM nor LSD affected the levels of CA in whole brain, LSD did not modify a-MT depletion of brain CA, APM enhanced norepinephrine depletion and decreased that of dopamine, LSD may act as a site structurally related to the doPamine receptor, 3 Fig. 3 Tab. 30 Ref. NAI0/PSH/NL Psychopharmacology Research Laboratory and Neuropharmacology Research Laboratory, Veterans Administration Hospital, Sepul- veda. California 91343, U.S.A..