Effect of minor tranquillisers on hippocampal θ rhythm mimicked by depletion of forebrain noradrenaline

Abstract

THERE are similarities between the behavioural effects of minor tranquillising drugs and those of lesions to the septal area and hippocampus¹. Since the septal area contains the pacemaker cells for the hippocampal theta rhythm², a parsimonious hypothesis to account for these common effects is that tranquillisers affect behaviour by altering septal control of this rhythm. Sodium amylobarbitone (SA) has been shown to block the behavioural effects of frustrative non-reward¹, as do septal³ and hippocampal⁴ lesions. Rats exposed to non-reward in the runway show a characteristic hippocampal θ response at 7.7 Hz (ref. 1) (the θ frequency range in the rat is about 6–12 Hz). Higher and lower frequencies occur during forms of behaviour which are unaffected by the drug. It has therefore been proposed¹ that the behavioural effects of SA arise by virtue of an impairment of septal control of the hippocampal θ rhythm specifically in a frequency band centred on 7.7 Hz. In support of this, it has been demonstrated⁵ that this drug raises the threshold for septal driving of the hippocampal θ rhythm selectively at 7.7 Hz, frequencies both above and below this value being minimally affected. Here we show that this kind of frequency-specific effect on septal driving of the hippocampal θ rhythm is also produced by other drugs with similar effects on behaviour¹ (ethanol, chlordiazepoxide and Δ⁹-tetrahydro-cannabinol (Δ⁹-THC)), by drugs which impair noradrenergic neural transmission, and by destruction of the dorsal ascending noradrenergic bundle by intracerebral injection of 6-hydroxydopamine (6-OHDA)⁶.