7-OH-DPAT, Unlike Quinpirole, Does Not Prime a Yawning Response in Rats

Repeated treatment in ontogeny with the dopamine (DA) D2/D3 receptor agonist quinpirole is associated with enhanced quinpirole-induced yawning and other behaviors such as vacuous chewing, vertical jumping, and antinociception. To determine if the reputedly DA D3 agonist (±)-2-(dipropylamino)-7-hydroxy-1,2,3,4-tetrahydronaphthalene (7-OH-DPAT) would prime for yawning in a manner analogous to that for quinpirole, rats were treated for the first 11 days after birth with an equimolar dose of either quinpirole or 7-OH-DPAT (195.4 nmol/kg/day) and tested for agonist-induced yawning in adulthood. While enhanced quinpirole-induced and 7-OH-DPAT-induced yawning was observed in quinpirole-primed rats, acute treatments with quinpirole and 7-OH-DPAT did not produce an enhanced yawing response in 7-OH-DPAT-\u27primed\u27 rats. Our findings indicate that 7-OH-DPAT, unlike quinpirole, does not prime for quinpirole- or 7-OH-DPAT-induced yawning in rats

Modulation of Central Dopamine Receptor Reactivity in the Rat, by Nitric Oxide Donors and Inhibitor: Behavioral Studies

Nitric acid has been implicated in a variety of physiological functions of the mammalian brain, and in a large number of its pathologies. Recently we have demonstrated that a nitric oxide donor (L-arginine) and a nitric-oxide-synthase-inhibitor (nitro-L-arginine-methyl-ester) modified the response of central al dopamine D 1 and D 3 receptors to some of their agonists. In the present study we demonstrate the modulatory effect of L-arginine, nitro-L-arginine-methyl-ester and molsidomine (another nitric oxide donor) on the reactivity of the central dopamine receptors to specific agonists and antagonists. The agonists tested were SKF-38393, 7-OH-DPAT and quinpirole, and the antagonists - SCH-23390 and haloperidol. They were evaluated in the rat by the following behavioral methods: locomotor activity, locomotor coordination, rearings and cataleptogenic activity (D 2 modulation); grooming time (D 1 activation); yawning (D 3 activation) and ethanol- and phenobarbital-sleeping-time parameters after SKF-38393 or quinpirole pretreatment. Our results suggest that nitro-L-arginine-methyl-ester is effective in modulating the reactivity of the central dopamine receptors D 2, D 1 and D 3, to their agonists and antagonists, and that it is much more effective than L-arginine in regulating the righting reflex after ethanol and phenobarbital, in both female and male mature rats

Amphetamine and mCPP Effects on Dopamine and Serotonin Striatal in Vivo Microdialysates in an Animal Model of Hyperactivity

In the neonatally 6-hydroxydopamine (6-OHDA)-lesioned rat hyperlocomotor activity, first described in the 1970s, was subsequently found to be increased by an additional lesion with 5,7-dihydroxytryptamine (5,7-DHT) (i.c.v.) in adulthood. The latter animal model (i.e., 134 μg 6-OHDA at 3 d postbirth plus 75 μg 5,7-DHT at 10 weeks; desipramine pretreatments) was used in this study, in an attempt to attribute hyperlocomotor attenuation by D,L-amphet-amine sulfate (AMPH) and m-chlorophenylpi-perazine di HCl (mCPP), to specific changes in extraneuronal (i.e., in vivo microdialysate) levels of dopamine (DA) and/or serotonin (5-HT). Despite the 98-99% reduction in striatal tissue content of DA, the baseline striatal microdialysate level of DA was reduced by 50% or less at 14 weeks, versus the intact control group. When challenged with AMPH (0.5 mg/kg), the microdialysate level of DA went either unchanged or was slightly reduced over the next 180 min (i.e., 20 min sampling), while in the vehicle group and 5,7-DHT (alone) lesioned group, the microdialysate level was maximally elevated by ∼225% and ∼450%, respectively - and over a span of nearly 2 h. Acute challenge with mCPP (1 mg/kg salt form) had little effect on microdialysate levels of DA, DOPAC and 5-HT. Moreover, there was no consistent change in the microdialysate levels of DA, DOPAC, and 5-HT between intact, 5-HT-lesioned rats, and DA-lesioned rats which might reasonably account for an attenuation of hyperlocomotor activity. These findings indicate that there are other important neurochemical changes produced by AMPH-and mCPP-attenuated hyperlocomotor activity, or perhaps a different brain region or multiple brain regional effects are involved in AMPH and mCPP behavioral actions

Locomotor Sensitization of Dopamine Receptors by Their Agonists Quinpirole and SKF-38393, During Maturation and Aging in Rats

Our laboratories have been investigating the reactivity of central dopamine D1 and D2/D3 receptors by their corresponding dopamine agonists (SKF-38393 and quinpirole), during development and aging in rats. By evaluating the number of oral movements (a parameter for D1 receptor activation after SKF-38393) and the number of yawns (as a parameter for D3 activation after quinpirole), we demonstrated that not only was there a dose-response activity for both drugs in the two parameters tested, but that the D3 activity was enhanced with the rats\u27 development and aging, due to life-long persisting D3 supersensitivity. In the present study we checked whether D2 and D1 receptors were also sensitized at old age, by measuring behavioral parameters characteristic to D2 (locomotor activity and rearings) and to D1 (grooming time). In the long-term study, male Wistar rats were challenged for 18 months with increasing doses of either SKF-38393, quinpirole or saline. At the age of 19 months they were given a single injection of either drug or saline. In the short-term study, male and female rats were given four single injections of either SKF-38393, quinpirole or saline, with one week intervals, and locomotor time and number of rearings recorded. Long-term quinpirole was found to induce supersensitivity of the D2 receptor complex, demonstrated by both enhanced locomotor time and rearing behavior, while long-term SKF-38393 treatment activated the D1 receptors, as evaluated by grooming time. Short-term quinpirole enhanced supersensitivity of the D2 receptors only in female rats, as assessed by increasing both locomotor time and rearing behavior, reiterating previous results on sex-dependent monoaminergic reactivity