Mary Jeanne Kallman

Hallucinogenic agents as discriminative stimuli: A correlation with serotonin receptor affinities

A choice between two levers in an operant chamber was used to train 24 rats, under a variable-interval 15 s schedule of sweetened milk reinforcement, to discriminate a hallucinogenic (psychotomimetic) agent, 5-methoxy-N,N-dimethyltryptamine (5-OMe DMT), from saline administration. The 5-OMe DMT stimulus generalized in a dose-related manner to each of 14 tryptamine related analogs. With the exception of one compound, the effective dose for the 5-OMe DMT response correlated highly (r=-0.86) with 5-HT receptor affinity (as determined using an isolated rat fundus preparation).

Superior colliculus involvement in the locomotor effects of ambient noise and the stimulants

Partial destruction of the superior colliculus (45%) significantly decreased the normal facilitatory effect of ambient white noise on locomotor activity levels in young rats. As recovery from surgery occurred and as test experience increased, the loss observed immediately following surgery was reduced. Presumably because of the age of the rats examined, destruction of the superior colliculus failed to potentiate the stimulant effects of d-amphetamine or methylphenidate on locomotion. These data suggest that the superior colliculus is involved in changes in general activity that result from manipulation of auditory stimuli in the environment in addition to the documented involvement of the superior colliculus in alterations of general responsivity resulting from manipulations of visual stimuli in the environment. Moreover, the superior colliculus is implicated in maintaining both excitatory and inhibitory changes in response to the environment of the organism.

The discriminative stimulus properties of the R2 isomer of viminol

Viminol is a pyrrylethanolamine derivative which exists naturally as a racemic mixture containing six different stereoisomers. Viminol has been reported to exert both potent analgesic activity and minimal dependence liability. The analgesic component of racemic viminol has been attributed to the R2 isomer, while the antagonistic S2 isomer appears to be responsible for minimizing the dependence liability of the racemate. We tested the R2 isomer of viminol in rats trained to discriminate 3 mg/kg morphine sulfate from saline on a VI-15 sec schedule for sweetened milk reinforcement. The R2 isomer resulted in dose dependent morphine-like responding, with complete generalization to the 2.5 mg/kg dose of R2 viminol. The morphine-like discriminative stimulus properties of R2 viminol were reversed by naloxone in a dose-dependent fashion, with total blockade by 0.1 mg/kg naloxone. R2 viminol, like morphine, also had a biphasic effect on response rate with low doses increasing and high doses suppressing response rates. R2 viminol had a overall shorter time course than that reported for morphine, and its different physiological and behavioral effects may not occur simultaneously. These data suggest that R2 viminol exerts a subjective effect similar to that of morphine and supports the hypothesis that R2 viminol has opiate activity despite its lack of structural relationship to the opiate series.

Efficacy of choice testing to predict chronic ingestion of drinking solutions adulterated with chemicals.

The feasibility of using a measure of palatability in a 2-bottle choice paradigm to determine detriments in fluid intake when unpalatable solutions containing drugs or chemicals were provided as a sole source of fluid was examined. Palatability measures obtained from testing various concentrations of quinine with water in a two-bottle choice paradigm were compared with intake of these same solutions when they were the sole fluid source for 20 consecutive days. Mice were observed to significantly avoid quinine solutions at concentrations as low as 0.0001 mg/ml in a choice situation while fluid intake was reduced in a forced drinking situation only at a concentration of 0.1 mg/ml. Palatability altered forced fluid intake only when quinine solutions comprised 20% or less of total intake in a choice situation. This approach was successfully employed to predict whether various concentrations of halogenated hydrocarbons could be administered in a repetitive forced drinking situation without reducing total fluid intake of mice.