Effects of B‐HT 920 on nigrostriatal and mesolimbic dopamine systems in normosensitive and supersensitive rats

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Abstract
B‐HT 920, a D2 dopamine receptor agonist, was tested for its ability to exert presynaptic actions in normosensitive rats, and for possible postsynaptic actions in rats made ‘supersensitive’ to apomorphine. In normosensitive rats, B‐HT 920 (0.01–0.3 mg kg−1, i.p.) increased dopamine concentrations and lowered metabolite levels to a similar extent in all four terminal regions examined (medial prefrontal cortex, olfactory tubercle, nucleus accumbens, caudate‐putamen). Analogous effects were seen for 5‐hydroxytryptamine and its metabolite 5‐hydroxyindoleacetic acid. Rats which received bilateral 6‐hydroxydopamine (6‐OHDA) infusions into the caudate‐putamen showed signs of postsynaptic dopamine receptor activation (stereotyped behaviour) in response to B‐HT 920 (0.1 and 1.0 mg kg−1, i.p.) and to apomorphine (0.2 mg kg−1, s.c.). Similarly, B‐HT 920 (0.1 mg kg−1) induced contralateral circling in rats that had received unilateral 6‐OHDA infusions into the medial forebrain bundle; the rate of circling increased gradually over several weeks. In contrast, bilateral 6‐OHDA infusions into the nucleus accumbens resulted in a supersensitive (locomotor stimulant) response to a low dose of apomorphine (0.1 mg kg−1, s.c.), but not to B‐HT 920 (0.01 and 0.1 mg kg−1). In intact rats, withdrawal of chronic haloperidol treatment induced behavioural supersensitivity to apomorphine but not to B‐HT 920.

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