Nicotinic receptors

Regulation of normal or abnormal behaviour is critically controlled by the central serotonergic systems. Recent evidence has suggested that serotonin (5-HT) neurotransmission dysfunction contributes to a variety of pathological conditions, including depression, anxiety, schizophrenia and Parkinson’s disorders. There is also a great amount of evidence indicating that 5-HT signalling may affect the reinforcing properties of drugs of abuse by the interaction and modulation of dopamine (DA) function. This chapter is focused on one of the more addictive drugs, nicotine. It is widely recognised that the effects of nicotine are strongly associated with the stimulatory action it exhibits on mesolimbic DAergic function. We outline the role of 5-HT and its plethora of receptors, focusing on 5-HT2 subtypes with relation to their involvement in the neurobiology of nicotine addiction. We also explore the novel pharmacological approaches using 5-HT agents for the treatment of nicotine dependence. Compelling evidence shows that 5-HT2C receptor agonists may be possible therapeutic targets for smoking cessation, although further investigation is required.peer-reviewe

Loss of Alternative Non-Drug Reinforcement Induces Relapse of Cocaine-Seeking in Rats: Role of Dopamine D1 Receptors

Animal models of relapse to drug seeking have focused primarily on relapse induced by exposure to drugs, drug-associated cues or contexts, and foot-shock stress. However, relapse in human drug abusers is often precipitated by loss of alternative non-drug reinforcement. The present experiment used a novel ‘resurgence' paradigm to examine relapse to cocaine seeking of rats as a result of loss of an alternative source of non-drug reinforcement. Rats were first trained to press a lever for intravenous infusions of cocaine. Next, cocaine deliveries were omitted and food pellets were provided for an alternative nose-poke response. Once cocaine seeking was reduced to low levels, food pellets for the alternative response were also omitted. Cocaine seeking increased with the loss of the alternative non-drug reinforcer (ie, resurgence occurred) despite continued extinction conditions. The increase in cocaine seeking did not occur in another group of rats injected with SCH 23390 before the loss of the alternative reinforcer. These results suggest that removal of an alternative source of reinforcement may induce relapse of cocaine seeking and that the dopamine D1 receptor may have a role in this effect

Dyskinesia-inducing lead contacts optimize outcome of subthalamic stimulation in Parkinson's disease

Acute dyskinesias elicited by STN-DBS, here referred to as stimulation-induced dyskinesias, predict optimal clinical outcome in PD. However, it remains elusive whether stimulation-induced dyskinesias can guide DBS programming