Nicotinic receptors are located in the hippocampus and their activation evokes neurotransmitter release (Gray et al. 1996). Local application of nicotine excites CA1 pyramidal neurones in vivo (Frazier et al. 1996). In the current study we investigated the effects of systemic administration of nicotine on the activity of single neurones in the CA1 and dentate gyrus (DG) regions.

All experiments were carried out in accordance with UK Home Office regulations (Animal (Scientific Procedures) Act). Male Sprague-Dawley rats (260-350 g) were anaesthetized with urethane (1.25 g kg^-1, I.P.) and spontaneously breathed room air. Single-unit activity of hippocampal neurones was recorded using glass electrodes filled with 2 M NaCl. Presumed CA1 pyramidal and DG granule neurones were identified by their location (Lambda +4.0-4.2 mm, lateral 2.5-3.0 mm, depth (from the brain surface) 2.5-3.0 mm for CA1 and 3.0-3.8 mm for DG, respectively) and by their action potential configuration. Animals were humanely killed at the end of the experiments. Cumulative doses of nicotine (2-512 µg kg^-1 I.V., 3 min inter-dose interval) dose-dependently increased CA1 neuronal activity in seven out of nine cells. Of the remaining two CA1 neurones, nicotine inhibited one and had no effect on the other. Nicotine also evoked short-lasting transient increases of the blood pressure in all seven animals. Although not all cells responded consistently, the increase in neuronal firing usually outlasted the transient increases in blood pressure. The mean increase in neuronal firing rate, measured after the second highest dose (256 µg kg^-1 cumulatively) was 1002 ± 495 % (whole group, n = 9 cells, mean ± S.E.M.) and the peak BP increase was 19 ± 3 mmHg (n = 7 animals). The one DG neurone studied showed a dose-dependent inhibition by nicotine, with a 83 % reduction of the baseline firing rate following the cumulative dose of 256 µg kg^-1. Single bolus injections of nicotine (64 or 128 µg kg^-1, I.V.) excited two and inhibited two of the four CA1 neurones tested and evoked inhibition in six out of eight DG neurones tested and had no effect on the remaining two. Phenylephrine, in contrast, at doses (10-60 µg kg^-1, I.V.) which evoked similar or larger increases in blood pressure, had no or smaller effects on the neurones tested (CA1, n = 3 and DG, n = 6).

In summary, the results demonstrate that systemic application of nicotine could either excite or inhibit CA1 neurones but predominantly inhibited DG neurones in anaesthetized rats. These nicotine-evoked neuronal responses are unlikely to be due to the accompanying changes in blood pressure.

Frazier, C.J., Rollins, Y.D., Hall, M.E., Young, D.A. & Rose, G.M. (1996). Brain Res. 727, 217-220.

Gray, R., Rajan, A.S., Radcliffe, K.A., Yakehiro, M. & Dani, J.A. (1996). Nature 383, 713-716.