volkensin and Cocaine-Related-Disorders

Studies have shown that the nucleus accumbens shell plays an integral role in the expression of psychostimulant-induced behavioural sensitization. Dopaminergic regulation of excitatory amino acid inputs in this region of the brain could be a key factor in the neural influence of this phenomenon. Alterations in the dopaminergic innervation patterns in the shell have been demonstrated in rats that received repeated cocaine injections. Furthermore, lesions of brain regions that send projections to the shell alter psychostimulant-induced locomotion, both acutely and in sensitization paradigms. A previous study from our laboratory demonstrated that lesions of the shell before repeated cocaine treatment decrease the locomotor response to cocaine during the induction phase of behavioural sensitization. To better understand the role of this brain region during the expression phase of behavioural sensitization, the present study examined the effects of two forms of cytotoxic lesions of the shell. Rats received a sensitization-inducing regimen of cocaine (bi-daily injections of 15 mg/kg i.p. for 5 consecutive days). Two days after the last injection, rats demonstrating behavioural sensitization received one of three bilateral microinjections into the shell: (i) 0.5 micro L 0.9% saline; (ii) 2.5 micro g/0.5 micro L ibotenic acid (which lesions the cell bodies at the injection site); or (iii), 0.5 ng/0.2 micro L of volkensin (a retrograde suicide transport lectin). Upon challenge with cocaine (15 mg/kg) 12 days after surgery, neither ibotenic acid- nor volkensin-lesioned rats showed any difference in their locomotor response compared with sham controls. These data indicate that bilateral shell lesions do not affect the long-term expression of behavioural sensitization in cocaine-sensitized rats.

Topics: Animals; Cocaine; Cocaine-Related Disorders; Dopamine; Drug Administration Schedule; Excitatory Amino Acids; Glycoproteins; Ibotenic Acid; Male; Motor Activity; N-Glycosyl Hydrolases; Nerve Degeneration; Neural Pathways; Neurons; Neurotoxins; Nucleus Accumbens; Plant Lectins; Rats; Rats, Sprague-Dawley; Ribosome Inactivating Proteins, Type 2; Synapses; Synaptic Transmission; Ventral Tegmental Area