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8 mai 2003
Pharmacol Biochem Behav
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Behavioral differences between selectively bred rats:
D1 versus D2 receptors in yawning and grooming
Jose R. Eguibar, Jose C. Romero-Carbente, Alejandro Moyaho
Instituto de Fisiolog§a , Benemerita Universidad Autonoma de Puebla, Mexico
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Introduction : Yawning is an infrequently occurring behavior and is therefore difficult to study. Our laboratory has produced two groups of SpragueÐDawley rats selected for high- (HY) and low-yawning (LY) frequency (Urba-Holmgren et al.1990). In previous studies, differences in yawning between HYand LY have been attributed to a possible alteration of the cholinergic or dopaminergic neurotransmission systems (Urba-Holmgren et al. 1990, 1993). Novelty-induced grooming is often higher in HY than in LY rats (Eguibar and Moyaho,1997), but little is known yet about the neurochemical mechanisms underlying grooming differences between both groups of rats (Eguibar and Moyaho 1997).
Yawning and grooming are apparently related behaviors since they tend to occur in stress-related contexts (Eguibar and Moyaho1997; Moyaho and Valencia 2002). In previous studies, it was shown that dopamine D1 receptors are involved in grooming (Molloy andWaddington 1987; Van Wimersma Greidanus et al. 1989; Drago et al. 1999), whereas D2 autoreceptors (Mogilnicka and Klimek 1977; Yamada and Furukawa 1980; Urba-Holmgren et al. 1982; Dourish and Cooper 1985) or D2 postsynaptic receptors (Morelli et al., 1986; Serra et al., 1986; Scheel-Kruger, 1986; Stahle 1992) bring about yawning. The circumstancethat HYand LY rats differ in two behaviors, which distinguish between D1 and D2 receptors, led us to investigate to what extent dopamine neurotransmission accounts for the concomitant presence of high numbers of yawns and grooms in HY rats. Specifically, we tested whether HY were more responsive than LY rats to the effect of SKF 38393, a D1 agonist (Setler et al. 1978), and quinpirole, a D2 agonist (Tsuruta et al. 1981).We also coadministered single doses of both drugs to test whether the facilitatory role that the stimulation of dopamine D1 receptors exerts on the behavioral expression ofD2 (Longoni et al. 1987) could explain the difference between the two groups of rats. [...]
Discussion : Although we applied consecutive doses of quinpirole andSKF 38393 to the same subjects, accumulative effects on the measured behaviors are unlikely since 48 h elapsed between doses. In addition, it is known that SKF 38393 does not generate behavioral tolerance (Neisewander et al., 1991). Moreover, the doseÐresponse curves of yawning and grooming do not fit the prediction that greater doses would be necessary to reinstate the initial effect (Carlton, 1983).The increment in the number and duration of grooming episodes with SKF 38393 in HY and LY rats is consistent with previous studies on other strains of rats (Braun andChase, 1987; Longoni et al., 1987; Molloy and Waddington,1987; Serra et al., 1990), and accords with the view that D1 receptor activation contributes to the initiation as well as the completion of grooming sequences (Berridge and Aldridge,2000).
The finding that HY and LY rats did not differ in the number or duration of grooming episodes in response to SKF38393 suggests that dopamine D1 receptors do not play a direct role in grooming between these groups of rats. Incontrast, the fact that quinpirole did not inhibit grooming episodes in HY rats as much as in LY rats suggests that D2 receptor activation can produce differences in grooming between the two groups of rats. Since the difference was restricted to the frequency of grooming episodes, it appears that quinpirole can distinguish between grooming frequency and duration.
Although the decrease in grooming episodes with quinpirole is consistent with previous studies (White etal., 1988; Eilam and Szechtman, 1989; Eilam et al., 1989,1992; Jackson et al., 1989, but see Braun and Chase, 1987;Walters et al., 1987), there are no previous reports, as far aswe know, in which quinpirole can affect differentially the frequency and duration of grooming episodes.The increment in yawning with quinpirole agrees with previous reports (Longoni et al., 1987; Spina et al., 1989;Kostrzewa and Brus, 1991). Similarly, the direction of the difference in yawning between HY and LY rats after the administration of quinpirole accords with studies that indicate that apomorphine and ( -)-3-PPP have a greater effect on HY than on LY rats (Urba-Holmgren et al. 1993). In thepresent study, HY and LY rats differed in yawning inresponse to low doses of quinpirole which primarily affect DA autoreceptors (Di Chiara et al., 1978). This agrees with the suggestion that yawning is an autoreceptor-mediated response, although D1 receptor activation may also be involved, as the inhibitory effect of SKF 38393 on yawning differed between HY and LY rats. In fact other studies havequeried the hypothesis that yawning is an autoreceptor mediated response (Stahle and Ungerstedt, 1986), and some authors have provided suggestive evidence for a role of dopamine D3 receptors in eliciting yawning (Kostrzewa and Brus, 1991; Damsma et al., 1993). Therefore, there is the possibility that differences in yawning frequency between HY and LY rats are the result of quinpirole activating D3 receptors.
On the other hand, there is evidence that dopamine D1 and D2 receptors are coupled (Arnt, 1985a,b), and that the stimulation of D1 receptors by endogenous dopamine exerts a facilitatory role in the behavioral expression of D2 receptor activation (Morelli et al., 1986; Braun and Chase, 1987;Longoni et al., 1987). According to this hypothesis, the coadministration of quinpirole and SKF 38393 would potentiate yawning. However, the results did not corroborate this prediction, as yawning was below the level reached when quinpirole alone was administered. Nor did the results agree with earlier studies which indicate that D1 receptor activation inhibits yawning induced by apomorphine (Zarkovsky andCereska, 1989) or by bromocriptine (Canales and Iversen,2000), a D2-class receptor agonist. Instead, our findings indicate that when coadministered, the effect of quinpirole acted against SKF 38393.In summary, the results presented here indicate that the activation of D2 receptors contributes to a greater extentt han is the case for D1 receptors to yawning and grooming differences between HY and LY rats.
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