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Pharmacological manipulations that alter dopamine (DA) at DA receptor subtypes produce reductions in feeding behaviour. What remains uncertain is the exact way in which these reductions in feeding are achieved as a consequence of differing drug actions at separate receptor subtypes. In this study our aim was to compare the anorectic effects of the preferential D3/D2 agonists 7-hydroxy-2-(di-n-propylamino)tetralin (7-OH-DPAT) and quinpirole and the non-selective D2/D3 antagonist raclopride on the microstructure of licking responses in non-deprived rats. In a 20-min test, trained adult, male hooded rats had access to one of three solutions: 1%, 3% or 10% sucrose. 7-OH-DPAT (0.1-1.0 mg/kg, i.p.), quinpirole (0.03-0.3 mg/kg, s.c.), raclopride (0.03-0.3 mg/kg, i.p.) or vehicle were injected 20 min prior to the start of the licking test. A lickometer recorded the timing of each lick, from which the microstructural parameters of bout frequency and bout duration were also computed. All compounds reduced the mean bout duration, while 7-OH-DPAT and raclopride also brought about a compensatory increase in bout number. Analysis of the licking rates over the test session showed that 7-OH-DPAT, quinpirole and raclopride decreased the initial rate, without affecting the rate of decline of licking. Changes in licking microstructure (i.e. initial rate of licking and mean bout duration) after the administration of 7-OH-DPAT, quinpirole and raclopride, are consistent with an action of these dopaminergic compounds to reduce palatability.

The cannabinoid receptor agonists delta9-tetrahydrocannabinol (delta9-THC) and HU-210 were compared in terms of their effects on: (1) progressive ratio (PR) responding for food, and (2) free food intake. In the first experiment, food-deprived Wistar rats were trained on a time-constrained (60 min) PR-5 schedule for food reinforcement, in which the response requirement incremented by five lever presses for each successive reinforcer. One group of rats received vehicle, 0.5, 1 or 3 mg/kg delta9-THC (i.p.), and three other groups received HU-210 (i.p.) at three different dose ranges, spanning 0.001-0.1 mg/kg. In the second experiment, the effects of the two drugs on free food intake were tested in a separate group of non-deprived rats. For PR responding, delta9-THC significantly increased the break point (final ratio completed) and the total number of lever presses emitted. The same drug also significantly increased free food intake. However, the effects of HU-210 were quite different: it did not alter PR responding at any dose; instead, its only significant effect was to reduce free food intake at 0.06 mg/kg. These data suggest that increased motivation to obtain food might underlie the hyperphagic effects of delta9-THC. However, the synthetic agonist HU-210 has different effects: it only acts to reduce feeding behaviour, an outcome that probably reflects non-specific behavioural disruption. These findings suggest important differences between the two CB1 receptor agonists in terms of their pharmacological effects.