D2-dopamine receptor and alpha2-adrenoreceptor-mediated analgesic response of quercetin.

Quercetin, a bioflavonoid (100-300 mg/kg) produced dose dependent increase in tail-flick latency, the analgesic effect being sensitive to reversal by naloxone (1 mg/kg). Prior treatment with haloperidol (1 mg/kg), D1/D2 receptor antagonist haloperidol, sulpiride (50 mg/kg), a selective D2 receptor antagonist, yohimbine (5 mg/kg), a alpha2-adrenoreceptor antagonist but not by SCH 23390 a, selective D1 receptor antagonist blocked this response. Apomorphine (1 mg/kg) a mixed D1/D2 dopamine receptor agonist, and quinpirole (0.5 mg/kg), a selective D2 receptor agonist also produced antinociception, that was reversed by haloperidol (1 mg/kg), sulpiride (50 mg/kg), but not by yohimbine (5 mg/kg). The antinociceptive action of quercetin (200 mg/kg) was potentiated by D2 agonist quinpirole (0.2 mg/kg). Dopamine D1 receptor agonist SKF38393 (10 and 15 mg/kg) failed to alter the antinociceptive effect of quercetin (200 mg/kg). Quercetin (200 mg/kg) reversed reserpine (2 mg/kg-4 hr) induced hyperalgesia, which was reversed by sulpiride but not by yohimbine. Thus, a role of dopamine D2 and alpha2-adrenoreceptors is postulated in the antinociceptive action of quercetin.

Effects of central imidazolinergic and alpha2-adrenergic activation on water intake

Non-adrenergic ligands that bind to imidazoline receptors (I-R), a selective ligand that binds to alpha2-adrenoceptors (alpha2-AR) and mixed ligands that bind to both receptors were tested for their action on water intake behavior of 24-h water-deprived rats. All drugs were injected into the third cerebral ventricle. Except for agmatine (80 nmol), mixed ligands binding to I-R/alpha2-AR such as guanabenz (40 nmol) and UK 14304 (20 nmol) inhibited water intake by 65 percent and up to 95 percent, respectively. The selective non-imidazoline alpha2-AR agonist, alpha-methylnoradrenaline, produced inhibition of water intake similar to that obtained with guanabenz, but at higher doses (80 nmol). The non-adrenergic I-R ligands histamine (160 nmol, mixed histaminergic and imidazoline ligand) and imidazole-4-acetic acid (80 nmol, imidazoline ligand) did not alter water intake. The results show that selective, non-imidazoline alpha2-AR activation suppresses water intake, and suggest that the action on imidazoline sites by non-adrenergic ligands is not sufficient to inhibit water intake

Midbrain adrenergic mechanisms modulating flight behaviour induced by hypothalamic stimulation.

The present study was carried out in ten cats of either sex. Flight response was obtained by electrical stimulation of dorsomedial regions of preoptic area (A13-14.5, L3.5 V-3.5 to -3.7) and lateral hypothalamic regions (A12.5, L2.5-3.5, V-3.7). It consisted of a goal directed attempt to get out of the cage with a vigorous leaping to foot. Norepinephrine when microinjected in 10 micrograms doses into pretectal area of midbrain (A3.5, 3.0, V+1.0 to +1.5 mm) significantly lowered the mean current strength from 640uA to 420uA; clonidine, an alpha-2 agonist in 5 micrograms dose when microinjected into the same locus also significantly lowered the mean current strength to the same level. On the other hand yohimbine, an alpha-2 blocker in 5 micrograms dose when microinjected in to the same locus significantly increased the mean current strength from 640 to 970 uA. These results indicate that hypothalamically induced flight response is mediated via the alpha-2 adrenoceptive mechanism operating at the midbrain level. Control microinjection of normal saline and propylene glycol in similar volumes failed to produce any changes in current strength.