Acute nicotine administration increases BOLD fMRI signal in brain regions involved in reward signaling and compulsive drug intake in rats.

Background: Acute nicotine administration potentiates brain reward function and enhances motor and cognitive function. These studies investigated which brain areas are being activated by a wide range of doses of nicotine, and if this is diminished by pretreatment with the nonselective nicotinic receptor antagonist mecamylamine.

Methods: Drug-induced changes in brain activity were assessed by measuring changes in the blood oxygen level dependent (BOLD) signal using an 11.

Attenuated methamphetamine-induced locomotor sensitization in serotonin transporter knockout mice is restored by serotonin 1B receptor antagonist treatment.

Repeated administration of methamphetamine (METH) enhances acute locomotor responses to METH administered in the same context, a phenomenon termed as 'locomotor sensitization'. Although many of the acute effects of METH are mediated by its influences on the compartmentalization of dopamine, serotonin systems have also been suggested to influence the behavioral effects of METH in ways that are not fully understood. The present experiments examined serotonergic roles in METH-induced locomotor sensitization by assessing: (a) the effect of serotonin transporter (SERT; Slc6A4) knockout (KO) on METH-induced locomotor sensitization; (b) extracellular monoamine levels in METH-treated animals as determined by in-vivo microdialysis; and (c) effects of serotonin (5-HT) receptor antagonists on METH-induced behavioral sensitization, with focus on effects of the 5-HT1B receptor antagonist SB 216641 and a comparison with the 5-HT2 receptor antagonist ketanserin.

Varenicline and cytisine diminish the dysphoric-like state associated with spontaneous nicotine withdrawal in rats.

Tobacco addiction is characterized by a negative mood state upon smoking cessation and relapse after periods of abstinence. Clinical studies indicate that negative mood states lead to craving and relapse. The partial α4/α6/β2* nicotinic acetylcholine receptor (nAChR) agonists varenicline and cytisine are widely used as smoking cessation treatments.

Transgenic mice in the study of drug addiction and the effects of psychostimulant drugs.

The first transgenic models used to study addiction were based upon a priori assumptions about the importance of particular genes in addiction, including the main target molecules of morphine, amphetamine, and cocaine. This consequently emphasized the importance of monoamine transporters, opioid receptors, and monoamine receptors in addiction. Although the effects of opiates were largely eliminated by mu opioid receptor gene knockout, the case for psychostimulants was much more complex.

[Side effects of opioid and gene variants].

There are individual differences in the analgesic effect and the side effect of the opioid to which genetic variation may be related. Analysis of micro-opioid receptor knockout mice indicated that inhibition of gastrointestinal transit by morphine is mediated by micro-opioid receptor. Our study suggested that gastrointestinal symptom (especially loss of appetite) as a side effect of opioid could be associated with the gene polymorphism of dopamine D2 receptor.