Previous data have shown that nicotine inhibits 5-hydroxytryptamine (5-HT) neuronal firing in the dorsal raphe nucleus (DRN) in vivo (Engberg et al. 2000). In the present study we investigated whether the α7 nicotinic receptor is involved in mediating this inhibitory effect using the selective α7 agonist 5Ì-phenylspiro[1-azabicyclo[2.2.2]octane-3,2Ì(3ÌH)-furo[2,3-b]pyridine] (Astra II).
Experiments were carried out in accordance with the Animal (Scientific Procedures) Act (1986). Male Sprague-Dawley rats (250-350 g, Harlan, UK) were anaesthetised with chloral hydrate (400 mg kg-1 I.P.; maintained with I.V. supplements via the lateral tail vein). A femoral artery was cannulated in order to record blood pressure. Body temperature was maintained at 37 ± 1°C throughout the experiment using a heating pad. Animals were placed in a stereotaxic frame, the scalp incised and a burr hole made in the skull (-7.8 mm from bregma, 1.5 mm lateral). Extracellular recordings were made using 2 M NaCl-filled single barrelled electrodes (1.5-3.5 M¢), stereotaxically lowered into the DRN at an angle of 15 deg from the vertical. DRN serotonergic cells were identified according to previously established criteria (Aghajanian et al. 1978). Their stable baseline firing was measured for at least 4 min before administration of 0.2 ml vehicle (saline) and cumulative doses of drug at 2 min intervals via the lateral tail vein. As additional confirmation of serotonergic cells, the effects of 8-OH DPAT and WAY100635, 5-HT1A receptor agonist and antagonist, respectively, were examined on some neurones. Animals were humanely killed at the end of the experiment.
Nicotine (10-320 µg kg-1) induced transient inhibition in one-third of 5-HT neurones tested (n = 6/18), and transient increases in blood pressure. Thus in the first minute after 160 µg kg-1 nicotine (n = 12) and in both the first and second minute after 320 µg kg-1 (n = 10), the firing rate was significantly reduced (ANOVA with post-hoc Dunnett’s test, P < 0.05). On the other hand, Astra II (4-256 µg kg-1) produced neither transient or prolonged changes in firing rate in the DRN (n = 7), nor increases in blood pressure. To examine effects of blood pressure increases per se, similar increases in blood pressure were induced by phenylephrine (8-60 µg kg-1 I.V.) but this resulted in an increase in DRN firing in the first minute (104.7 ± 9.5 % of baseline; mean ± S.E.M., n = 7).
These data suggest that the inhibitory effect of nicotine on serotonergic neurones of the DRN is unlikely to be mediated by α7 nicotinic receptors or indirectly via blood pressure changes.
- Aghajanian, G.K., Wang, R.Y. & Baraban, J. (1978). Brain Res. 153, 169-175.
Engberg, G., Erhardt, S., Sharp, T. & Hajos, M. (2000). Naun. Sch. Arch. Pharmacol. 362, 41-45.