In vitro morphine metabolism by rat microglia.

Morphine is mainly transformed to morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) in the liver. Glucuronidation is also performed by rat brain homogenates and UDP-glucuronosyltransferases (UGTs) are present in the brain. Here we investigated the possibility that microglia transforms morphine into its metabolites M3G and M6G.

Effects of the 5HT2C antagonist SB242084 on the pramipexole-induced potentiation of water contrafreeloading, a putative animal model of compulsive behavior.

Rationale: In rats, quinpirole, a dopaminergic D2/D3 receptor agonist, elicits both hyperdipsia and water "contrafreeloading" (CFL), a putative model of compulsivity. The role of D3 receptors in this effect remains unclear. Clomipramine (CIM) was found to contrast both hyperdipsia and CFL, but the role of serotonin in this effect requires further investigation.

Repeated exposure to codeine alters morphine glucuronidation by affecting UGT gene expression in the rat.

We have previously found that phenantrenic opioids, such as heroin or naltrexone, modulate morphine glucuronidation in the rat. Here we further investigated the effects of phenantrenic opioids on morphine glucuronidation comparing the effects of codeine and heroin. In particular, we measured the synthesis of morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) from morphine: in the liver microsomal preparations obtained from rats repeatedly treated with two different doses of codeine (ex vivo study); in primary cultures of rat hepatocytes previously incubated for 72h with codeine, or heroin (in vitro study); in the latter conditions, the levels of expression of genes coding for uridine-5'-diphosphate-glucuronosyltransferases (UGTs) A1, A6, A7 and 2B1 were also determined; finally, the levels of glucuronic acid in rat hepatocytes previously incubated for 72h with codeine or heroin were assessed.

Clomipramine, but not haloperidol or aripiprazole, inhibits quinpirole-induced water contrafreeloading, a putative animal model of compulsive behavior.

Rationale: Repeated administrations of the D2/D3 agonist quinpirole (QNP) to rats elicit an antieconomical pattern of drinking called "contrafreeloading" (CFL), a putative model of compulsive-like behavior.

Objectives: We tested the sensitivity of QNP-induced CFL to haloperidol (HAL), aripiprazole (ARI), and clomipramine (CIM), the latter proven effective in the treatment of obsessive-compulsive disorder (OCD).

Methods: Rats were trained under a schedule of reinforcement (FR3) for water.

The effects of clozapine on quinpirole-induced non-regulatory drinking and prepulse inhibition disruption in rats.

Rationale: The biological underpinnings of schizophrenic polydipsia are poorly understood.

Objectives: This study is aimed at fulfilling the requisites of an experimental model of this syndrome through the quinpirole (QNP) induction of non-regulatory drinking in rats.

Methods: In a first experiment, clozapine (10 and 40 mg/kg p.

Opposite roles of dopamine and orexin in quinpirole-induced excessive drinking: a rat model of psychotic polydipsia.

Rationale: Repeated administration of the dopamine D2/D3 agonist quinpirole (QNP) progressively increases non-regulatory water intake. This effect may model psychotic polydipsia, a potentially fatal but poorly understood condition.

Objectives: The growing evidence for a role of orexin in mediating arousal and cognition has linked this peptide to schizophrenia, hence we examined whether manipulations of dopaminergic and orexinergic systems, as well as of setting, would further characterize the model.