Behavioural pharmacology of nicotine: implications for multiple brain nicotinic receptors

Behavioural studies can contribute to the characterization of receptors for psychoactive drugs, and attempts have been made to link behavioural effects of nicotinic agonists with the high affinity binding site for [3H] nicotine. Cueing (discriminative stimulus) effects of drugs enable trained humans or animals to recognize when a specific drug is administered. There was a correlation between the potencies of some compounds in the binding procedure and their ability to produce the nicotine discriminative stimulus in rats, supporting the view that the high affinity binding site was a functional receptor. Nicotine also produced complex changes in locomotor activity of rats, characterized acutely by transient depression and chronically by persistent stimulation. The abilities of nicotinic compounds to produce these locomotor effects were not always consistent with the studies on binding and the nicotine discriminative stimulus. Some compounds were relatively more potent in producing locomotor depression or stimulation than the discriminative effect. Some compounds also failed to produce chronic locomotor activation at doses that produced discriminative and acute depressant effects. These findings may be interpreted as preliminary evidence that different behavioural effects of nicotine may be mediated through different mechanisms, possibly involving multiple subtypes of nicotinic receptors.