Brain Mechanisms

Chemical stimulation is of more use than is electrical stimulation, for it is selective and only affects well-defined circuits. Moreover, chemical blockade is a more appropriate process than knife-cuts or electro-coagulation, which "knock out"' everything. Therefore, chemical manipulations in the brain surely give more information than do other more aggressive but less specific and less selective interventions. As a consequence, anatomically overlapping, but functionally quite differing, circuits can be distinguished rather easily by means ot specific chemical stimulation (or inhibition). And this may well be the reason why lesion and (or) electric stimulation experiments necessarily had to lead to Adams's sophisticated, but hardly informative, deduction that "motivating stimuli activate pathways that converge upon sets of homogeneous neurons, called the motivational mechanism, whose activity determines the motivational state of the animal". As a matter of fact, converging stimuli may be of quite opposite polarity: one may be the stimulus governing the reaction directly (a cholinergic one, in this case), while the other may be a modulatory one (adrenergic, in this case); and the latter will determine the final, already restricted, motivational output. According to our experience, a given behavioral pattern, actually the so-called aggressive behavior, can be "switched" from one form to another (e.g. from offense to defense or vice versa) in two ways:

Switching mechanism 1. The neurotransmitter originally involved (acetylcholine, in this case) is also liberated in structures as yet unaffected by it; for instance, at receptors in the limbic system or at nonmuscarinergic receptors within the hypothalamus itself (T -receptors, see below).

Examples of 1. (a) Cholinergic stimulation of well-defined regions of the amygdala inhibits, or fully antagonizes, the ADR evoked by cholinergic stimulation of the hypothalamus (Decsi and Nagy 1974). (b) Stimulation of the hypothalamus with d-tubocurarine in one hemisphere counteracts the ADR evoked by simultaneous CCh-stimulation of the contralateral hypothalamus (Decsi, Varszegi, and Mehes 1969).

Switching mechanism 2. The action of the neurotransmitter originally involved (acetylcholine, in this case) will be modified (suppressed) by increased tone in another neurotransmitter system (adrenergic, in this case) in the region in question, or by that ot some other area also involved in circuitry of the reaction.

Examples ot 2. (a) Prior injection 01 noradrenaline in the thalamus suppresses the ADR evoked by subsequent CCh stimulation of the same region (Decsi and Nagy 1977a). (b) Injection of noradrenaline in the thalamus (intralaminary cell groups) counteracts the ADR evoked by cholinergic stimulation of the hypothalamus (Decsi and Nagy 1977b).

Both mechanisms require very few "extra" inputs (e.g. local ones in the hypothalamus, red nucleus, etc), or additional inputs from, or through, the limbic system (e.g. hippocampus or amygdala; Nagy and Decsi 1974; Decsi and Nagy 1974).

Escape (fear) reaction ot the cat. The term "fear and escape reaction" has been used by us to describe the characteristic behavior that can be evoked by direct topical stimulation ot the hypothalamus with d-tubocurarine (Decsi and Karmos-Varszegi 1969). Our first results have been corroborated by the experiments of Romaniuk, Brudzinsky, and Gronska (1973) The most characteristic external signs of the reaction were summarized as follows (Decsi and Karmos- Varszegi 1969) "High degree of restlessness, walking and running around in the cage Repeated attempts to escape from the cage; the animal tears the floor with the claws, jumps against the wall and even against the top of the cage Once out of the cage the cat hides at the most remote corner of the room and, when approached, runs terrifiedly away to look for some other hiding place"

Since d-tubocurarine is a cholinomimetic drug, it is plausible to assume that this reaction is also cholinergic in character. However, the reaction is not brought about by stimulation of receptors belonging to either the M- or N-type; in this case a third type of cholinergic receptor had to be assumed to be present in the brain (T -receptors) resembling those found in the neuromuscular junction (Decsi, Varszegi, and Mehes 1969; in this connection, see also Myers 1974). Thus, the behavioral manifestation that we have called tear and escape reaction is cholinergic as to its neurotransmitter organization. This reaction seems to participate in the complex of "offense, defense, and submission" The d- tubocurarine-induced (cholinergic) escape should represent a part of the defense, but certainly not the last step of it, since the final stage of any defense must necessarily be an attack (or counter-attack), be it ever so hopeless. From a transmitter point of view, this might mean a switch from T -receptors to M- receptors, or releasing M-receptors from a continuous adrenergic modulatory control (Intraspecific submission is quite another question; it might represent increased catecholaminergic input to overpower the original cholinergic defense behavior).

Adams speaks about three motivational systems, with modulators, releasing and directing stimuli involved in each. At first sight, such a classification in terms of just three (or better two) groups seems to be an oversimplification; and, by themselves, the terms "modulators, releasing and dIrecting stimuli" do not say much either. However, when we try to reduce these systems to a common denominator on the basis of their possible neurotransmitter organization, they fit surprisingly well with the data obtained in neuropharmacological investigations. All the hypothesized motivational systems seem to work with cholinergic neurotransmission, while the chemical basis ot the modulatory, releasing and directing stimuli is most probably catecholaminergic