Population pharmacokinetics and safety of AZD1446, a neuronal nicotinic receptor agonist, administered in healthy volunteers.

AZD1446 is a highly selective agonist of central α4β2 and α2β2 neuronal nicotinic receptors. The compound has been shown to improve cognition in preclinical studies and thus has potential for treatment of cognitive disorders, including Alzheimer's disease (AD). This report presents the pharmacokinetics of AZD1446 based on a pooled population pharmacokinetic analysis of five studies in Caucasian and Japanese healthy volunteers.

Naltrexone attenuates amphetamine-induced locomotor sensitization in the rat.

Amphetamine, and other stimulants, readily induces behavioral sensitization, an effect hypothesized to reflect neurobiological changes that may underlie certain aspects of drug addiction. Apart from the effects on the dopamine system, previous studies have also shown that amphetamine interacts with other neurotransmitters, including the endogenous opioid system. The unselective opioid receptor antagonist naltrexone (NTX) modulates amphetamine-induced effects in both laboratory animals and humans.

The effect of naltrexone on amphetamine-induced conditioned place preference and locomotor behaviour in the rat.

Whereas amphetamine and other psychostimulants primarily act on the dopamine system, there is also evidence that other neurotransmitter systems, such as the endogenous opioid system, modulate psychostimulant-induced effects. Several studies have investigated the role of opioid antagonists on cocaine-induced conditioned place preference (CPP), but there is limited information about the interaction with amphetamines. The aim of the present study was to investigate the effect of the opioid receptor antagonist, naltrexone (NTX) on the conditioning, expression and reinstatement of amphetamine-induced place preference.

The opioid receptor antagonist naltrexone attenuates reinstatement of amphetamine drug-seeking in the rat.

Amphetamine produces its rewarding effects by enhancing dopamine transmission in the mesocorticolimbic pathway. Several studies have also suggested the involvement of the endogenous opioid system in mediating the neurochemical and behavioural effects of amphetamine. The aim of this study was to investigate the effect of the unselective opioid receptor antagonist naltrexone (NTX) on reinstatement of amphetamine self-administration in the rat.

Ethanol alters the effect of kappa receptor ligands on dopamine release in the nucleus accumbens.

Repeated exposure to ethanol has previously been shown to induce alterations in both midbrain dopamine and dynorphin systems. The aim of this study was to investigate functional changes in the sensitivity of dynorphin/kappa-receptor systems following repeated ethanol administration, using dopamine as an indirect marker. The effects of kappa-opioid receptor ligands on dopamine release in the rat nucleus accumbens were investigated following repeated ethanol administration (2 g/kg body weight, twice daily for 7 days).

Running increases ethanol preference.

Wheel running performed by rats is reinforcing, rewarding and possibly addictive. In this study we analyzed if wheel running could affect ethanol preference. Lewis rats, known to be both addiction-prone and to develop an excessive wheel running behavior, were given access to ethanol in a two-bottle free-choice paradigm.

Nociceptin/orphanin FQ tissue concentration in the rat brain. Effects of repeated ethanol administration at various post-treatment intervals.

The aim of this study was to study short- and long-term effects of repeated ethanol administration on nociceptin/orphanin FQ (N/OFQ) tissue concentrations in rat brain with radioimmunoassay. Animals were given either ethanol (intraperitoneal) or saline for 13 consecutive days. N/OFQ levels were examined at 30 min, 5 days and 21 days after the last dose on day 13.