Long-lasting nicotinic modulation of GABAergic synaptic transmission in the rat nucleus accumbens associated with behavioural sensitization to amphetamine.
A robust increase in dopaminergic transmission in the nucleus accumbens (NAc) shell has been reported to be consistently associated with the long-term expression of behavioural sensitization to drugs of abuse. However, little is known about how this affects the neuronal network of the NAc. We made cellular recordings in NAc slices of saline- and amphetamine-pretreated adult rats and found that expression of behavioural sensitization was associated with long-lasting changes in the basal firing pattern of cholinergic interneurons up to 3 weeks after the last drug injection. Consequently, upon amphetamine sensitization, an inhibiting effect of the nicotinic receptor blocker mecamylamine on the amplitudes of spontaneous GABAergic synaptic currents as well as on the failure rate of electrically evoked GABAergic currents was found that was not present under control conditions. Thus, behavioural sensitization to amphetamine is associated with an up-regulation of the endogenous activation of nicotinic receptors that, in turn, stimulate the GABAergic synaptic transmission within the NAc shell. This is a new mechanism by which drugs of abuse may induce alterations in the processing and integration of NAc inputs involved in psychomotor sensitization.
de Rover
Mischa
M
Department of Experimental Neurophysiology, Institute for Neurosciences (INW), Centre for Neurogenomics and Cognitive Research, Vrije Universiteit, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands.
Mansvelder
Huibert D
HD
Lodder
Johannes C
JC
Wardeh
George
G
Schoffelmeer
Anton N M
AN
Brussaard
Arjen B
AB
D000109:Acetylcholine / Q000378:metabolism; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D009433:Neural Inhibition / Q000187:drug effects; D009474:Neurons / Q000145:classification / Q000187:drug effects / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects*; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects*; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000697:Central Nervous System Stimulants; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D005680:gamma-Aminobutyric Acid; D008464:Mecamylamine; D009538:Nicotine; D000661:Amphetamine; D000109:Acetylcholine