The Effects of Some Drugs when Injected Directly into the Brain

Abstract

A review has been made of the properties of agents with possible transmitter function, and of various methods used to administer agents directly into the brain. In particular, a method is described for the administration of agents directly into the cerebral ventricles of conscious rats. Using this method, a number of possible transmitters have been administered and their effects upon the behaviour of rats described. Also, the effects of these agents are the effects of some of their antagonists on body temperature are compared with the effects of nuorphine given intraventricularly. It is possible that morphine mediates its effects on body Seperavins through alterations in central levels of acetylcholine (ACh) and noradrenaline (Na). The effects of possible transmitters given intraventricularly on "the nociceptive threshold of conscious rats have also been studied, as have their efiects upon the anti-nociceptive effects of morphine. Morphine is potentiated by intraventricularly injected 5-hydroxytryptamine (5-HT) and antagonised by intraventricular NA. A previously observed efiect, that reserpine antagonises the anti-nociceptive effect of morphine, has been confirmed. This effect of reserpine was reduced by the intraventricular injection of 5-HT, but not NA, The effect of reserpine on morphine may be due to a central depletion of 5-HT rather than of NA. Experiments with cholinergic agents and both narcotic and narcotic-antagonist agents suggest that analgesics of both types depend upon a cholinergic link within the central nervous system; in contrast, tryptaminergic and adrenergic links appear to be important only in the narcotic agents, Intraventricular infusion experiments suggest that 5-HT and NA may be involved in the genesis of morphine tolerance and/or dependence. A few experiments have involved the placement of agents in more discrete areas of the brain, in an attempt to localise their effects. A number of previously recorded effects were seen again in this study, for example hyperphagia and body temperature changes. In contrast, effects upon the nociceptive threshold were limited. The involvement of NA, 5-HT and ACh in the mediation of temperature regulation, and in altering the nociceptive threshold, has been discussed; so too has the interaction of these agents with morphine. A possible basis for tolerance and/or dependence in the rat is outlined.