raclopride and Hypothermia

Methamphetamine (METH) induces hyperthermia in warm and hypothermia in cool environments. Our first goal was to further study the role of ambient temperature in METH's effect on core temperature in rats. Previously, these effects were primarily demonstrated in high doses; we extended this investigation to the low-dose range (1 mg/kg METH). Our second goal was to identify the role of the D2 receptor in METH's effects in cool ambient temperatures.. Rats received METH (saline, 1, 5, and 10 mg/kg), raclopride (saline, 0.3, 0.6, and 1.2 mg/kg), or a combination (all doses of raclopride combined with 10 mg/kg METH). Treatments occurred in ambient temperatures of 18, 24, or 30 °C.. Consistent with prior research, 5 and 10 mg/kg METH caused hyperthermia or hypothermia in a dose- and ambient temperature-dependent manner (60 min after METH). In contrast, 1 mg/kg produced similar levels of hyperthermia at all ambient temperatures. These findings suggest that a threshold METH dose exists; below this dose, METH still changes core temperature, but CNS control over temperature regulation is left intact. In our experiments regarding D2 blockade, raclopride decreased METH-induced core temperature at 30 and 24 °C (60 min after METH), consistent with previous findings. We extended these findings by demonstrating that in a cool ambient temperature (18 °C), raclopride pretreatment also lowered the core temperature response to METH. Although the D2 receptor is known to mediate hypothermia, the combination of METH and D2 blockade suggests a complex mediation of the core temperature response, perhaps involving neurotransmitter interactions.

Topics: Animals; Body Temperature; Dopamine Agents; Dopamine Antagonists; Dopamine D2 Receptor Antagonists; Dose-Response Relationship, Drug; Fever; Hypothermia; Male; Methamphetamine; Raclopride; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D2; Temperature

The objective of this study was to examine possible interactions between serotonergic and dopaminergic agents lowering core temperature via stimulation of 5-HT1A and dopamine (DA) D2 receptors, respectively. The effects of the 5-HT1A receptor agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin HBr (8-OH-DPAT) and the DA D2/3 receptor agonist 7-OH-DPAT on core temperature was monitored in adult male Wistar rats, approximately 300 g body weight. The temperature probe was connected to a PC-assisted temperature instrument, and an automated printer device was activated when the temperature reading had stabilized (+/-0.1 degrees C) for 10 s. As expected, 7-OH-DPAT [0.5 and 2.0 micromol x kg(-1) subcutaneous (s.c.)] as well as 8-OH-DPAT (0.15-2.4 micromol x kg(-1) s.c.), produced a dose-dependent hypothermia. When combined, there were additive effects of the two compounds, although the effects of 7-OH-DPAT were attenuated by 8-OH-DPAT at the higher doses (0.6-2.4 micromol x kg(-1)), in all probability because of emerging DA D2 receptor blocking properties of the latter compound.

Topics: 8-Hydroxy-2-(di-n-propylamino)tetralin; Animals; Body Temperature; Dopamine Agonists; Hypothermia; Male; Raclopride; Rats; Rats, Wistar; Receptors, Dopamine D2; Receptors, Dopamine D3; Receptors, Serotonin; Receptors, Serotonin, 5-HT1; Serotonin Receptor Agonists; Tetrahydronaphthalenes

The dopamine D3/D2 receptor agonists 7-OH-DPAT, quinpirole, quinelorane, and PD128907, the mixed dopamine agonist apomorphine, the D2 agonist bromocriptine, and the D1/D5 agonist SKF38393 were examined in models of hypothermia and prepulse inhibition (PPI) in Wistar rats. As dopamine agonist-induced hypothermia has been proposed as a model of D3 receptor function, and dopamine agonists are known to disrupt PPI, drug potencies to induce hypothermia were established and compared with doses necessary to disrupt PPI. 7-OH-DPAT, quinpirole, quinelorane, PD128907, and apomorphine, reduced body temperature and disrupted PPI with a similar rank order of potency (quinelorane > quinpirole = 7-OH-DPAT > PD128907 = apomorphine). Bromocriptine and SKF38393 were ineffective in both models. In a separate study, the dopamine reuptake inhibitors cocaine and GBR 12909 had no effect on PPI. In a final set of studies, the D2/D3 antagonist raclopride blocked both 7-OH-DPAT-induced hypothermia and 7-OH-DPAT-induced PPI disruption. The 5-HT1A antagonist WAY 100,135, and the peripheral D2-like antagonist domperidone had no effect. These findings suggest that the hypothermia and PPI disruptions seen with some of these dopamine agonists may be mediated by central D3 receptors; however, only studies using more selective dopamine receptor ligands can definitively rule out effects at the D2 or D4 receptors.

Topics: Animals; Body Temperature; Cocaine; Domperidone; Dopamine Agonists; Dopamine Antagonists; Dopamine Uptake Inhibitors; Hypothermia; Male; Piperazines; Raclopride; Rats; Rats, Wistar; Receptors, Dopamine D2; Receptors, Dopamine D3; Reflex, Startle; Salicylamides; Serotonin Antagonists

Clozapine (7.5-30.0 mumol kg-1 s.c.) produced a decrease in core temperature in the rat. The temperature decrease caused by clozapine (7.5 mumol kg-1 s.c.) was fully antagonized by the selective dopamine D1 receptor antagonist SCH 23390 (0.3 mumol kg-1) s.c.) and a partial antagonism was obtained by the selective dopamine D2 receptor antagonist raclopride (1.6 mumol kg-1 s.c.). On the other hand, the hypothermia was not antagonized by alpha-adrenoceptor antagonists (idazoxan and prazosin), 5-HT receptor antagonists ((-)-pindolol and ritanserin) or by the muscarinic M1 receptor antagonist scopolamine. The hyperthermia produced by the 5-HT1C/2 receptor agonist DOI (0.75 mumol kg-1) was blocked by clozapine (3.0 mumol kg-1 s.c.). Clozapine did not antagonize hypothermia produced by selective dopamine D1 and D2 receptor agonists (A 68930 and quinpirole), the alpha 2-adrenoceptor agonist clonidine, the 5-HT1A receptor agonist 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) or the muscarinic M1 receptor agonist oxotremorine. The present results suggest that clozapine may be a partial agonist at brain dopamine D1 receptors.

Topics: Amphetamines; Animals; Benzazepines; Body Temperature; Body Temperature Regulation; Chromans; Clonidine; Clozapine; Dopamine Agents; Dopamine D2 Receptor Antagonists; Ergolines; Hypothermia; Injections, Subcutaneous; Male; Oxotremorine; Quinpirole; Raclopride; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D1; Salicylamides; Serotonin Antagonists