Quinpirole- and amphetamine-induced hyperdipsia: influence of fluid palatability and behavioral cost.

Daily administration of moderate doses of amphetamine or of the dopaminergic D2 agonist quinpirole is associated with the development of excessive, non-regulatory drinking. Here we compared the influence of manipulating fluid palatability and behavioral cost on the development of this drinking augmentation. Experiment 1 was based on the phenomenon of contrafreeloading (CFL): animals work for a resource even though the same resource is freely available. The effects of 15 daily injections of amphetamine (1.0 and 1.7 mg/kg i.p. ) or quinpirole (0.1 and 0.56 mg/kg i.p.) were evaluated in mildly water-deprived rats. For the first 6 days the rats obtained water by lever pressing (FR3) only; over the following 9 days water was also freely available (CFL). Initially, 0.56 mg/kg quinpirole reduced lever pressing for water. A complete recover of responding was then obtained, and was followed by a progressive increment in the amount water obtained by lever pressing during the CFL phase (from 10 to 50%). Amphetamine did not affect percent CFL, but at the highest dose (1.7 mg/kg) reduced total water intake during the last 3 days of treatment. In experiment 2 the rats had free access to two bottles, one of which contained tap water, and the other contained either an ethanol (6%) or a sucrose (5%) solution. After habituation to this regimen, the rats received 10 daily i.p. injections of vehicle, amphetamine (1.0 or 3 mg/kg), or quinpirole (0.1 or 0.56 mg/kg). Quinpirole 0.56 mg/kg enhanced daily fluid intake under both sucrose and ethanol conditions, but selectively reduced ethanol preference. The higher amphetamine dose reduced fluid intake and sucrose preference. In conclusion, chronic exposure to a dopaminergic D2 agonist, but not to amphetamine, produced an increment of drinking that was resistant to manipulation of either palatability or the behavioral cost of the fluid.

Acamprosate does not antagonise the discriminative stimulus properties of amphetamine and morphine in rats.

Acamprosate (calcium acetylhomotaurinate) is a GABA derivative that prevents drinking relapses in a significant number of alcoholics. Since little is known about the interaction of acamprosate with other addictive drugs, we studied the effects of this agent (as sodium salt) in two groups of rats trained to discriminate, respectively, morphine (1.7 mg kg(-1)i.p.) or amphetamine (0.5 mg kg(-1)i.p.) from solvent in a two-lever fixed ratio 30 operant behaviour reinforced by water access. Accordingly to the finding that acamprosate inhibits the action of excitatory aminoacids, its effects were compared with those of dizocilpine (MK-801), an NMDA antagonist. Results show that acamprosate (170 and 320 mg kg(-1)i.p. ) produced a slight, and not significant, shift to the left of generalization curves of both morphine and amphetamine without affecting response rates. In contrast, MK-801 potentiated response rate effects of both morphine and amphetamine without affecting their generalization curves. As far as discriminative stimuli participate in the relapsing process of addiction, our results do not predict a role of acamprosate in the prevention of amphetamine or morphine abuse relapsing.

Amphetamine reinstates polydipsia induced by chronic exposure to quinpirole, a dopaminergic D2 agonist, in rats.

The hypothesis that the combined activation of D1 and D2 dopaminergic receptors is instrumental in inducing amphetamine (AMPH)-mediated hyperdipsia was tested in rats. The D1 agonist SKF-38393 (SKF) and the D2 agonist quinpirole (QNP) were i.p. injected, alone or in combination, to male rats for 10 days. After 2 days of wash-out, a single dose of AMPH (3 mg/kg) was administered. Intake of water and food and diuresis were daily measured at 2, 5 and 24 h. In two further experiments the higher dose of QNP (0.56 mg/kg) was given with two different doses of the D1 antagonist SCH-23390 (SCH), or, respectively, of the peripheral D2 antagonist domperidone (DMP). In a fourth experiment, the possibility that QNP, given alone or in combination with SKF, produces an AMPH-like internal state was evaluated by using a drug-discrimination paradigm. Results show that chronic administration of QNP produced a significant increase of 24 h water intake that was reinstated by AMPH. This QNP effect was only partially prevented by DMP, suggesting a main central mechanism of action. By itself D1 receptor manipulation did not affect water intake, but influenced QNP polydipsia that, accordingly, was enhanced by the lower dose of SKF (0.3 mg/kg) and inhibited by the lower dose of SCH (0.01 mg/kg). In rats trained to discriminate AMPH from solvent, QNP partially generalized for the AMPH stimulus, an effect that was potentiated by SKF. In conclusion, a D1-modulated sensitization of D2 dopaminergic mechanisms is probably involved in AMPH-induced hyperdipsia.

[Insulin resistance in obese and non-obese patients with polycystic ovary syndrome. Possible role in the pathogenesis of the disease]. / L'insulinoresistenza nelle pazienti con sindrome dell'ovaio policistico (PCOs) obese e non obese. Possibile ruolo nella patogenesi della malattia.

The pathogenesis of Polycystic Ovary Syndrome (PCOs) is not well known till now. Previous reports indicated an hyperinsulinemia and insulin resistance in obese and non obese PCOs. However the role of hyperinsulinemia in PCOs pathogenesis is not completely understood. In this study we evaluated the glycemic and insulinemic response to OGTT in 21 women suffering from PCOs (13 obese and 8 normal weight) and in 16 fertile women as a control group (8 obese and 8 normal weight). All tested women showed normal glycemia before and after OGTT. Basal insulinemia in PCOs was similar to that observed in control group. Mean insulinemic levels following OGTT in obese control group and in PCOs were significantly higher than those observed in normal women (p < 0.05). Insulin area under curve (AUC) following OGTT in non obese PCOs was significantly higher than that observed in non obese control women (72442.13 +/- 18668.9 mUI/ml/h versus 53710.8 +/- 83365 mUI/ml/h; p = 0.02), but lower than that observed in obese PCOs (192793 +/- 49421; p < 0.001). In obese PCOs insulin AUC was significantly higher than that observed in obese control group (138836.8 +/- 28800.9; p = 0.012). Insulin AUC was positively related to BMI in control group (p < 0.001) but not in PCOs. In PCOs group insulin AUC was positively related to hirsutism degree (p = 0.032) and circulatory levels of T (p = 0.044), LH (p < 0.001) and E1 (p = 0.026).(ABSTRACT TRUNCATED AT 250 WORDS)