Behavioural Pharmacology of Dopamine D2 and D3 Receptors: Use of the Knock-out Mice Approach

Since the first evidence that dopamine (DA) serves as a central neurotransmitter became available (Carlsson et al. 1958), this catecholamine has generated enormous interest among neuroscientists, and would probably qualify as the most studied central neurotransmitter. Its pivotal role in numerous physiological processes (Jaber et al. 1996) and in major pathological conditions, in particular psychoses (Snyder 1976), has certainly contributed greatly to this privileged status. It appeared fairly early that the effects of DA are mediated by at least two types of receptors, named the D1 and the D2 receptors (Kebabian and Calne 1979). This conclusion was based on the dissociated effects that stimulation of each type had on the activity of adenylate cyclase, the enzyme responsible for the production of cyclic adenosine monophosphate (c-AMP). Levels of c-AMP are increased by activation of D1 receptors (Kebabian and Calne 1979) and decreased by activation of D2 receptors (De camilli et al. 1979). This opposite role of the two types of DA receptors is not ubiquitous, as they have also been shown to act in a cooperative manner in several models (see Waddington 1989 for review). For example, the two subtypes act synergistically to promote locomotor activity when activated (Molloy et al. 1986) or to produce catalepsy when blocked (Klemm and Block 1988).