OLFACTORY PROJECTION SYSTEMS, DRUGS AND BEHAVIOR - REVIEW

(1) Bilateral olfactory bulbectomy (OB) produces a series of behavioural changes in the rat, characterised by hyperactivity and hyper-reactivity. It also produces an elevation of plasma 11-hydroxycorticosterone (11-OHCS). (2) Chronic treatment (10-14 days) of OB rats with anti-depressant drugs (amitriptyline, mianserin, viloxazine, nomifensine and iprindole) normalises the behavioural change and the 11-OHCS elevation. The mono-amine oxidase inhibitor, tranylcypromine, does not normalise these parameters. (3) Using two behavioural parameters (step-down avoidance testing and irritability), plus 11-OHCS measurements, it has proved possible to differentiate between anti-depressants, anti-anxiety agents, tranquilisers and central stimulants. OB therefore has potential as a screening method for differentiating between various classes of psychotropic drugs. (4) The quadracyclic anti-depressant, mianserin, proved negative in standard anti-depressant screening and a new derivative, GB-6582 proved positive in the OB model. GB-6582 is an efficient inhibitor of 5-hydroxytryptamine (5-HT) uptake. (5) The neurotoxin, 5-6 DHT, will mimic the behavioural and physiological effects of bulbectomy as will 5-7 DHT with prior treatment of the rat with desmethyl-imipramine, when these neurotoxins are injected directly into the olfactory bulb. The neurotoxin, 6-OHDA, injected into the bulb does not mimic the effects of OB. (6) GB-6582 when injected into the bulb prior to intra-bulbar 5-6 DHT, prevents the appearance of the behavioural and physiological effects of bulbectomy. (7) All the anti-depressants which normalise surgical bulbectomy, show the same effect with chemical bulbectomy induced by 5-6 DHT. (8) Following bulbectomy, neuroanatomical studies demonstrated degenerating fibres in: (a) the anterior hippocampus; (b) the corticomedial nucleii of the amygdala; (c) the bed nucleus of the stria terminalis and (d) the pre-optic area of the hypothalamus. (9) These brain areas are concerned with behavioural arousal, hypothalamic-adrenohypophyseal modulation and sexual behaviour. All these are adversely affected by bulbectomy. (10) The significance of these observations is discussed in terms of 5-HT-catecholamine interaction in the development of diseases of affect. © 1979.