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-'primed' rats. Our findings indicate that 7-OH-DPAT, unlike quinpirole, does not prime for quinpirole- or 7-OH-DPAT-induced yawning in rats.

Nitric oxide (NO) has been implicated in large number of pathologies and in normal physiological function of the brain. The aim of this study was to recognize the effect of Nitro-L-Arginine Methyl Ester ·HCl (NAME) and L-Arginine Ethyl Ester.HCl (ARGININE) on reactivity of the central DA D3 receptor to agonist (Quinpirole) in rats. For this reason we have been used specific behavioural procedure such yawning behaviour which is mediated via central DA D3 receptors. Experiments were perform in adult male Wistar rats treated daily with quinpirole (0.05 mg/kg IP) or vehicle (0.9% NaCl) for the first 11 days from birth to obtain of the central D3 receptor supersensitivity. NAME and ARGININE in different way modified response of the central DA receptor to quinpirole estimated by means yawning behavioural procedure.

It is known that dopamine (DA) receptors can be sensitized by repeated treatments with quinpirole during postnatal development. This study was undertaken to determine whether low-dose quinpirole treatments might sensitize receptors to quinpirole-induced yawning behavior. Rats were treated with quinpirole HCl (50 μg/kg per day) or saline at four different periods of ontogeny: a) the 10th day of gestation to day of birth; b) 1st-11th days after birth; c) 12th-22nd days from birth; or d) 23rd-33rd days from birth. The numbers of yawns occuring in 1 h after a challenge dose of quinpirole HCl (50 μg/kg, IP) was determined at 6 weeks. Rats exposed prenatally to quinpirole demonstrated increased numbers of yawns following the third dose of quinpirole (2-day interval between doses). In rats exposed postnatally to quinpirole, there was a 70-300% increase in the yawning response, with the greatest response occuring in the group treated with quinpirole from birth to 11 days from birth. The findings demonstrate that quinpirole receptors are sensitized by a low dose of quinpirole, 60-fold lower than previously shown. It is suggested that sensitized receptors are of the DA D3 subclass.

Yawning in male rats is a behavior that may be induced by a group of dopamine receptors when low doses of dopamine-receptor agonists are administered. To determine whether agonist treatments during postnatal development could produce a long-lived supersensitization of these dopamine receptors, rats were treated daily for the first 28 days from birth with quinpirole HCl (3.0 mg/kg/day, IP), an agonist that acts at D2 and D3 receptors. At 8 to 10 weeks from birth the dose-effect curve for quinpirole-induced yawning demonstrated that a supersensitization of dopamine receptors for yawning behavior had occurred. Yawning at the optimal dose of quinpirole HCl (100 μg/kg, IP) was increased 2-fold. The Bmax and Kd for D2 receptor binding in rat striatum were unaltered in this group of rats. These findings indicate that dopamine receptors can be ontogenically "primed" or supersensitized, and that the phenomenon apparently is not related to changes in striatal D2 receptor binding characteristics.

Repeated treatments of rats with the dopamine (DA) D2 receptor agonist quinpirole, consistently produce long-lived DA D2 receptor supersensitization, by the process that has been termed priming. Rats so-primed in ontogeny behaviorally demonstrate adulthood enhancement of low-dose quinpirole-induced yawning. Because 1) dopaminergic neurons originate in midbrain nuclei (substantia nigra and ventral tegmental area), and 2) noradrenergic neurons originate in pontine (locus coeruleus) and medullary areas, it might be presumed that these two monoaminergic systems are independent, not interdependent. However, in the present study we demonstrate that there was an attenuation of quinpirole-enhanced yawning at 8 weeks in rats that were 1) primed by repeated neonatal quinpirole HCl treatments (50 μg/kg per day SC) during the first ten days of postnatal ontogeny, and 2) lesioned at 3 days after birth with DSP-4 (N-2-chloroethyl-N-ethyl-2-bromobenzylamine hydrochloride, 50 mg/kg SC). Dose-effect curves indicated a 23-45% reduction in yawning by DSP-4 treatment of quinpirole-primed rats, acutely treated as adults with quinpirole (25, 50, or 100 μg/kg). Effectiveness of DSP-4 is reflected by the 95% and 99% reductions in norepinephrine contents of frontal cortex and hippocampus, respectively (HPLC/ED method). The findings are supportive of a modulatory role of noradrenergic fibers on dopamine receptor priming (supersensitization) in rat brain.

Driving while drowsy is a major cause behind road accidents, and exposes the driver to a much higher crash risk compared to driving while alert. Therefore, the use of assistive systems that monitor a driver’s level of vigilance and alert the fatigue driver can be significant in the prevention of accidents. This thesis introduces three different methods towards the detection of drivers’ drowsiness based on yawning measurement. All three approaches involve several steps, including the real time detection of the driver’s face, mouth and yawning. The last approach, which is the most accurate, is based on the Viola-Jones theory for face and mouth detection and the back projection theory for measuring both the rate and the amount of changes in the mouth for yawning detection. Test results demonstrate that the proposed system can efficiently measure the aforementioned parameters and detect the yawning state as a sign of a driver’s drowsiness.

Driving while drowsy is a major cause behind road accidents, and exposes the driver to a much higher crash risk compared to driving while alert. Therefore, the use of assistive systems that monitor a driver’s level of vigilance and alert the fatigue driver can be significant in the prevention of accidents. This thesis introduces three different methods towards the detection of drivers’ drowsiness based on yawning measurement. All three approaches involve several steps, including the real time detection of the driver’s face, mouth and yawning. The last approach, which is the most accurate, is based on the Viola-Jones theory for face and mouth detection and the back projection theory for measuring both the rate and the amount of changes in the mouth for yawning detection. Test results demonstrate that the proposed system can efficiently measure the aforementioned parameters and detect the yawning state as a sign of a driver’s drowsiness.

Driving while drowsy is a major cause behind road accidents, and exposes the driver to a much higher crash risk compared to driving while alert. Therefore, the use of assistive systems that monitor a driver’s level of vigilance and alert the fatigue driver can be significant in the prevention of accidents. This thesis introduces three different methods towards the detection of drivers’ drowsiness based on yawning measurement. All three approaches involve several steps, including the real time detection of the driver’s face, mouth and yawning. The last approach, which is the most accurate, is based on the Viola-Jones theory for face and mouth detection and the back projection theory for measuring both the rate and the amount of changes in the mouth for yawning detection. Test results demonstrate that the proposed system can efficiently measure the aforementioned parameters and detect the yawning state as a sign of a driver’s drowsiness.

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.

Dopamine (DA) receptor supersensitivity refers to the phenomenon of an enhanced physiological, behavioral or biochemical response to a DA agonist. Literature related to ontogenetic aspects of this process was reviewed. Neonatal 6-hydroxydopamine (6-OHDA) destruction of rat brain DA neurons produces overt sensitization to D1 agonist-induced oral activity, overt sensitization of some D2 agonist-induced stereotyped behaviors and latent sensitization of D1 agonist-induced locomotor and some stereotyped behaviors. This last process is unmasked by repeated treatments with D1 (homologous "priming") or D2 (heterologous "priming") agonists. A serotonin (5-HT) neurotoxin (5,7-dihydroxytryptamine) and 5-HT2C receptor antagonist (mianserin) attenuate some enhanced behavioral effects of D1 agonists, indicating that 5-HT neurochemical systems influence D1 receptor sensitization. Unlike the relative absence of change in brain D1 receptor number, DA D2 receptor proliferation accompanies D2 sensitization in neonatal 6-OHDA-lesioned rats. Robust D2 receptor supersensitization can also be induced in intact rats by repeated treatments in ontogeny with the D2 agonist quinpirole. In these rats quinpirole treatments produce vertical jumping at 3-5 wk after birth and subsequent enhanced quinpirole-induced antinociception and yawning. The latter is thought to represent D3 receptor sensitization. Except for enhanced D1 agonist-induced expression of c-fos, there are no changes in the receptor or receptor-mediated processes which account for receptor sensitization. Adaptive mechanisms by multiple "in series" neurons with different neurotransmitters may account for the phenomenon known as receptor supersensitivity.