ArticlesPermissive Role of Dopamine D2 Receptors in the Hypothermia Induced by Δ9-Tetrahydrocannabinol in Rats
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Animals
Male Sprague-Dawley rats weighing 125 to 150 g were used (Charles River, Calco, Como, Italy). Prior to experiments they were housed in group cages and kept at a temperature of 22° ± 1°C at 55% of humidity. Food and water were freely available and animals were maintained under an artificial 12/12 h light/dark schedule with light on from 0800 to 2000 h.
The experiments were carried out in accord to the recommendations of the declaration of Helsinki and to the European Communities Council Directive
Results
The administration of Δ9-THC caused a dose-dependent reduction in body temperature (Fig. 1). The maximum decrease obtained at doses of 2.5 and 5 mg/kg, respectively was 2.42 ± 0.42 and 2.92 ± 0.24°C, and occurred 60 min after treatment. The dose of 1 mg/kg had no effect (Fig. 1). As expected, and consistent with previous results (19), the hypothermic response to Δ9-Tetrahydrocannabinol (5 mg/kg) was totally antagonized by the CB1 cannabinoid receptor antagonist SR 141716A (0.5 mg/kg), given 20
Discussion
The results of the present study confirm previous observations showing that Δ9-THC reduces body temperature 7, 10, 11, 12, 19 and that this effect is reversed by the CB1 cannabinoid receptor antagonist SR 141716A 5, 19. Moreover, our results indicate that Δ9-THC–induced hypothermia is antagonized by the D2 dopamine receptor antagonists S(-)-sulpiride and S(-)-raclopride and, conversely, is potentiated by the D2 dopamine receptor agonists (-)-quinpirole and (+)-bromocriptine. When given alone at
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2022, Advances in PharmacologyCitation Excerpt :However, knowledge of this receptor is limited, and future work should investigate this possibility. In addition, serotonergic 5-HT1A receptors and dopamine D2 receptors also regulate Δ9-THC-induced hypothermia in an opposing manner such that D2 receptor antagonists attenuate and 5-HT1A receptor antagonists potentiate Δ9-THC's hypothermic effects and vice versa with their respective agonists (Malone & Taylor, 2001; Nava, Carta, & Gessa, 2000). Although Δ9-THC has no direct binding affinity at 5-HT1A and D2 receptors, these effects could be mediated indirectly via Δ9-THC metabolite activity at the 5-HT1AR and CB1-D2 heterodimer interactions.
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2014, Pharmacology Biochemistry and BehaviorCitation Excerpt :Ghozland et al. (2002) suggested that these effects may be a function of THC-induced hypothermia (mediated through kappa activity). THC's effects on temperature have been well characterized (Schmeling and Hosko, 1976, 1977; Fennessy and Taylor, 1978; Malone and Taylor, 1998; Nava et al., 2000), and drug-induced hypothermia has been suggested to mediate the aversive effects of several compounds, including nicotine and alcohol (Cunningham et al., 1988, 1992; Rinker et al., 2008, though see 2011). To address strain differences in THC-induced hypothermia and their possible relationship with THC-induced taste avoidance learning, the present study also examined the effects of THC on core body temperature at doses effective in inducing taste avoidance in the two strains.
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2011, NeuroscienceCitation Excerpt :The present findings also indicated that the inhibitory effect of 0.5 μg/rat of WIN on memory formation was significantly decreased by intra-BLA microinjection of SCH23390 or sulpiride, when given 5 min before post-training intra-CA1 administration of WIN. Previously, other investigators have found that Δ9-tetrahydrocannabinol-induced analgesia (Carta et al., 1999) and hypothermia (Nava et al., 2000a) can be potentiated and reversed by the dopamine receptor agonists (quinpirole and bromocriptine) and the antagonists (sulpiride and raclopride), respectively. The present results are in line with the reports which show that the amygdala is critically involved in modulating memory processes in the hippocampus (Almaguer-Melian et al., 2003; Tsoory et al., 2008).