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Hypotheses are presented on neural peculiarities of the monkey brain that distinguish monkeys from other mammals and man: The unique feature of cortical tissue is that it can be applied serially. It fulfils some requirements of a powerful visual system. The richness of visual as compared to other signals has yielded a basis for recognizing the bodily similarity of oneself to conspecifics. A visuo/motor coupling trained on oneself but applied to conspecifics ("aping") evolved. Long series of (generalized visuo/visual) computations feasible in a very large cortex would produce excessive delays that would not correspond to outer world delays. The new human solution to this is an "offline" system in which temporal relationships are described by excitation patterns. This gives rise to a rapid expansion of the cortex. In humans, a "meaning" has to be attributed to the mutual (computational) relationships of excitation patterns in the offline system, by a reference to the corresponding relationships that would be valid in the normal (online) system. "Perception" is a corollary of this. The offline treatment of time, together with "aping", leads to new types of helping and other social interactions. Monkeys may be compared to humans not using their offline system in the state of "absent-mindedness". Experimental approaches departing from excitation patterns are discussed.

Administration of imipramine, which blocks noradrenergic, serotonergic and cholinergic reuptake, to rats for 4 days counteracts the shuttlebox escape failures otherwise seen in rats which have been exposed to inescapable shock (the "learned helplessness" model of depression). The effects of the more selective reuptake inhibitors talsupram (noradrenergic), citalopram (serotonergic) and the anticholinergic compound scopolamine were assessed alone and in combination after acute or 4 days' administration on escape behavior. Their possible synergistic effects when combined with imipramine were also assessed. Talsupram and citalopram were ineffective, whereas scopolamine counteracted the escape failures. Combinations of talsupram, citalopram and a subeffective dose of scopolamine were ineffective. A synergistic effect was only seen when scopolamine was combined with a suboptimal dose of imipramine. Thus, the effect of imipramine on "learned helplessness" might rely partly on its anticholinergic component. However, as an acute high dose of imipramine (25 mg/kg) was ineffective [unlike the acute administration of scopolamine (0.12 mg/kg)], this drug retains a pharmacological effect which is not mimicked by scopolamine alone or by combining the specific reuptake inhibitors with scopolamine.

Some years ago it was considered that GABA "the major inhibitory transmitter in the CNS" inhibited the activity of the dopamine systems. Today it is evident that the GABA-dopamine interaction is considerably more complex, and in several recent reviews we have discussed that a reevaluation of previous experiments is obviously needed to test whether GABA physiologically may directly inhibit dopamine neuronal activity (43, 45, 49, 50). In this communication will be discussed some of the behavioural functions of GABA studied by the local intracerebral injection technique in rats. We have recently obtained evidence that GABA in the striato-entopeduncular, striato-nigral and the pallido-subthalamic descending GABAergic pathways is mediator of dopamine dependent behaviours related to dopamine receptor stimulation in striatum. The specific GABA agonist muscimol induced strong amphetamine-like stimulation and stereotyped behaviour in the nucleus entopeduncularis (EP) (the medial or inner segment of globus pallidus), the subthalamic nucleus (STN) and the zona reticulata of substantia nigra (SNR) (49, 50). GABA receptor stimulation in EP, STN and SNR mediates according to this new hypothesis the efferent output of striatum (see Fig. 1). This hypothesis may explain the findings that the systemic injection of GABA-facilitating drugs increases the stereotyped licking/gnawing behaviour induced by high doses of dopamine stimulants in rodents (43, 46) and worsens schizophrenic symptoms in the clinic (5, 52).

A local injection of kainic acid (KA) into the dorsal raphe nucleus (NRD) increased the motor activity and produced head shakes, hind limb abduction, forepaw treading and sniffing. This syndrome was antagonized partly by cyproheptadine and completely by naloxone. An injection of KA into the median raphe nucleus (NRM) produced sedation, catalepsy and analgesia, which were accompanied by a decrease in the beta-endorphin immunoreactivity in the mesencephalon. Naloxone completely reversed the behavioral inhibition after KA injections into the NRM, while a pretreatment with cyproheptadine augmented the catalepsy. KA injected into the NRD and NRM depressed the forebrain level of serotonin and slightly elevated that of 5-hydroxyindoleacetic acid. The results demonstrate that besides serotonin the opioid system is also involved in various effects induced by activation of the raphe nuclei.