Reticular stimulation and hippocampal theta rhythm in rats: effects of drugs.

The effect of drugs on hippocampal theta rhythm induced by high frequency stimulation of the midbrain reticular formation was investigated in free-moving rats. The linearity of the relationship between the frequency of theta produced and the intensity of the stimulating current was unchanged by injections of sodium amylobarbitone; however, the frequency itself was reduced. Choline@ blockade or depletion of noradrenaline, dopamine or serotonin levels in brain did not produce such a reduction in frequency, nor did they change the linearity of the function. These results contrast with the nonlinear effects which have been found with sodium amylobarbitone when septal stimulation is used to evoke theta rhythm; and with the fact that such nonlinear effects can be reproduced by depletion of forebrain noradrenaline levels. Sodium amylobarbitone appears, therefore, to affect control of hippocampal theta rhythm by actions on two systems, only one of which is dependent on noradrenaline. The duplication of behavioural effects of the drug by lesions of the dorsal ascending noradrenergic bundle may imply that the frequency at which theta occurs is less important for the control of such behaviours than other aspects of this electrical activity. GRAY (1970; 1972) has proposed that sodium amylobarbitone influences behaviour by altering the septal control (STUMPF, 1965) of hippocampal theta rhythm in a middle frequency band (7.7 Hz in the rat). Confirmation of the physiological part of this hypothesis comes from work with septal stimulation and hippocampal recording. Low frequency stimulation of the medial septum will drive hippocampal theta rhythm (BROCKE, PEDXHE, PILLAT & DEISENHAMMER, 1959), and in the free-moving rat the threshold current required to elicit such driving is minimal at 7.7 Hz (GRAY & BALL, 1970; JAMES, MCNAUGHTON, RAWLINS, FELDON & GRAY, 1977). GRAY & BALL (1970) found that sodium amylobarbitone eliminated this minimum by raising thresholds selectively in the region of 7.7 Hz. As might be predicted from the similarities between the behavioural effects of the barbiturates, benzodiazepines and ethanol (GRAY, 1977), this effect is also produced by injections of chlordiazepoxide and ethanol (MCNAUGHTON, JAMES, STEWART, GRAY, VALERO & DREWNOWSKI, 1977). This specific effect in the region of 7.7 Hz is not reproduced by manipulation of the cholinergic, serotonergic or dopaminergic systems (MCNAUGHTON et al., 1977), while it is produced by both systemic injections which deplete noradrenergic systems and neurotoxic lesions of the dorsal ascending noradrenergic bundle (GRAY, MCNAUGHTON, JAMES & KELLY, 1975; MCNAUGHTON et al., 1977). The full range of hippocampal theta frequencies can also be produced by high frequency stimulation of the midbrain reticular formation (GREEN dt ARDUINI, 1954), but the frequency of theta produced is monotonically related to the stimulation intensity (SAILER & STUMPF, 1957). STUMPF (1965) reported that hexobarbitone reduced the frequency of such theta rhythm, while scopolamine, although it could produce total blockade of theta, did not affect frequency. He did not report any frequency-specific effects of the drugs. Septal and reticular elicitation differ, then, as to whether frequency specific effects can be observed, both in control curves and in effects produced by injections of barbiturates. One possible source of discrepancy lies in the use of free-moving rats for the septal experiments and urethane-anaesthetized rabbits for the reticular ones. Other evidence makes this less likely. JAMES et al. (1977) reported linear reticular control curves and KRAMIS, VANDERWOW & BLAND (1975) reported a reduction in frequency with pentobarbital in the free-moving rat. However, KRAMIS et al. (1975) did not report the drug effect systematically with respect to frequency, and it is possible, therefore, that the barbiturates produce a change which is not linearly related to frequency. This paper reports a more detailed analysis of the linearity of the stimulation intensity-theta frequency data previously reported by JAMES et al. (1977) and investigates the effects on this function of injections