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.

Date of Award	Jul 1970
Original language	English
Awarding Institution	Aston University