Simultaneous radiotelemetric monitoring of the effect of D2-like dopamine receptor ligands on core temperature and home-cage activity in rats

O. Elekes and I. Gyertyán

Department of Behavioural Pharmacology, Gedeon Richter Ltd., Budapest, Hungary

The D2-like dopaminergic receptors play an important role in thermoregulation and motor behaviour. However, due to lack of selective ligands the functions of D2 and D3 receptors are still to be established. D3 receptor preferring agonists such as 7-OH-DPAT or PD-128907 were found to cause hypothermia and hypoactivity in rodents. The preferential D3 antagonist U-99194A induced increase in locomotor activity. It is assumed that these effects result from the action on postsynaptically localized D3 receptors. However, changes in body temperature and in motor activity usally are measured in separate studies, often applying diverse doses of the agonist or antagonist compounds. Simultaneuos monitoring of the the two parameters by radiotelemetry, a technique obviating stressful interventions, could yield comparable and more reliable data while attempting to clarify the role of the dopamine receptor subtypes in these behaviours.

In our experiments we used a six-channel Mini-Mitter TR-3000 telemetry system and measured the body temperature and home cage activity of male Wistar rats weighing 200-220 g at the beginning of the experiment.

The D3 antagonist U-99194A at a dose of 12 mg/kg sc. significantly increased the home cage activity of the animals without exerting any effect on body temparture. At doses of 0.1-0.3-0.5 mg/kg sc. (±)7-OH-DPAT elicited dose-dependent, significant hypothermia with maximal effect of -2 °C. The effect produced by the 0.5 mg/kg dose was not attenuated by 12 mg/kg sc. U-99194A. None of the tested doses of 7-OH-DPAT had any effect on spontaneous activity of the habituated rats; however, after concomittant adminstration with U-99194A a clear increase in home cage activity was registered. At 0.5 mg/kg sc. dose (±)PD-128907 induced 0.5 °C hypothermia. This mild, but significant hypothermia was partially inhibited by co-administration of U-99194A. Similarly to 7-OH-DPAT, PD-128907 did not alter the activity of the animals, but given together with U-99194A hyperactivity was observed.

Since U-99194A shows high selectivity to the D3 subtype it seems reasonable to assume - in accordance with the literature - that the molecule exerted its observed activity via D3 receptors. However, the two supposedly D3 preferring agonist did not influence the activity of rats in the dose range in which they produced hypothermia. This lack of effect together with the fact that the antagonist was still able to induce hyperactivity in rats treated with the agonist molecules, suggests that D3 receptors were unaffected by 7-OH-DPAT or PD-128907. The ineffectiveness of U-99194A against the hypothermia induced by 7-OH-DPAT also points out the absence of D3 receptors in the action of the agonist compund. Contradictory to the above conclusion, the fact that U-99194A was able to inhibit the hypothermia elicited by PD-128907, a compound with higher D3 selectivity than 7-OH-DPAT, suggest the involvement of D3 receptors in the hypothermic action of PD-128907.


Poster presented at Measuring Behavior 2000, 3rd International Conference on Methods and Techniques in Behavioral Research, 15-18 August 2000, Nijmegen, The Netherlands

© 2000 Noldus Information Technology b.v.