Methods for nicotine selfadministration 921 Surgical Techniques

One of the main issues in carrying out drug self-administration studies is the surgical implantation of catheters to permit drug delivery into the circulatory system. In our laboratory, catheters are prepared from a combination of silicone rubber and polyethylene tubing full details about design and construction have been reported.16 Figure 9.1 shows the structure of the catheter schematically. The silicone tubing is the end that is implanted into the circulatory system, in this case, the...

Creation And Maintenance Of Cell Lines Stably And Heterologously Expressing nAChR Of Defined Subunit Composition

Cell lines naturally expressing some important known nAChR subtypes have not yet been identified. In the case of nAChR subtypes found in the brain, this may be because mature, post-mitotic neurons have lost their susceptibility to neoplastic transformation, which may only occur in proliferating cells. This circumstance may change with advances in neuronal stem cell science and in creation of neuronal cell lines from transgenic animals in which oncogene expression is driven by neuron-specific...

Autonomic Nervous System

Antisense oligonucleotides to the a3 subunit were used by Listerud et al. (1991) to illustrate that functional nAChRs in chick sympathetic neurons are largely composed of a3-containing receptors. Removal of surface receptors using bromoacetylcholine, followed by incubation with a3 antisense for 48 hours, led to a > 90 reduction in channel activity compared with control cells. Antisense to a4 had no affect on nAChR channel conductance or kinetics. Removal of the a3 subunit with antisense also...

Computerized Assessment

The principal computerized test found useful for determining nicotine effects on cognitive function in adults with ADHD is the Conners continuous performance test (CPT).5,6 To characterize possible effects on other aspects of neurobehavioral function, components of the Automated Neuropsychological Assessment Metrics (ANAM) battery have also been used simple reaction time, spatial mental rotation, and delayed matching to sample.3435 The Conners CPT has been validated as an assessment tool for...

In Vitro Electrophysiological Approaches

Discussion of electrophysiological methods is presented elsewhere in this volume. In this section our discussion is limited to some general comments on the approach and a summary of major findings. Because nerve endings are too tiny to record from (with the exception of certain calyces41) presynaptic nAChR activity is inferred from a modulation of transmitter release detected as postsynaptic currents. Nicotinic modulation at glutamate and GABA synapses has been the major focus of this...

Abt594

Recently, a derivative of epibatidine, ABT-594 has been developed by Abbott Laboratories as a nicotinic analgesic and, as mentioned earlier, is currently in phase II clinical trials. ABT-594 shows similar affinity to epibatidine at the human a4p2 subtype (Ki of 37 and 42 pM for ABT-594 and epibatidine, respectively), but has 4000 times less activity at the neuromus-cular receptor.77 The systemic administration of ABT-594 produced broad-spectrum antinociceptive activity in preclinical assays of...

The Mnemonic Effects Of Mecamylamine In Monkeys

Administration of nicotine in experimental animals has been reported to facilitate neurotransmitter release and synaptic transmission in thalamo-cortical, ascending mesolimbic-dopaminergic, noradrenergic, and cholinergic pathways.3233 To what extent any of these effects contributes to nicotine's cognitive-enhancing action is not known. However, the concentrations of nicotine required to elicit receptor up-regulation34-36 or increased neurotransmitter release32,37 require M concentrations....

Tourettes Syndrome Nicotine And Animal Models

Tourette's disorder (TD) is a neuropsychiatry disorder with childhood onset that is characterized largely by the expression of sudden, rapid and brief, recurrent, non-rhythmic, stereotyped motor movements (motor tics) and sounds (vocal tics) that are experienced as irresistible, but can be suppressed for varying lengths of time.1 These motoric symptoms range from relatively mild to very severe over the course of a patient's lifetime.23 Most patients with TD also exhibit comorbid neuropsychiatry...

NAChR Localization

While the functional pharmacology approach provides strong evidence for the nicotinic modulation of transmitter release, the limited number of subtype-selective tools and a general lack of knowledge about the subunit composition of native nAChR have constrained the information generated about which nAChR subtypes are involved. Moreover, the precise localization of nAChR (for example in relation to synapses) cannot be addressed. Therefore techniques that map the anatomical localization of nAChR...