Long‐lasting nicotinic modulation of GABAergic synaptic transmission in the rat nucleus accumbens associated with behavioural sensitization to amphetamine

Abstract

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.

Nicotinic modulation of neuronal networks: from receptors to cognition

“…The putative presence of cholinergic interneurons in the PFC introduces the possibility of nicotine-induced ACh release independent of release from cholinergic terminals that originate from lower brain areas. Because the PFC is implicated in behavioral sensitization (see below), intrinsic properties of cholinergic interneurons and ACh release in the PFC could also be modified during behavioral sensitization, as we found in the NAc (de Rover et al 2004). Figure 1a shows a putative rodent PFC circuitry and locations of nAChRs as found in the PFC (Alkondon et al 2000;Lambe et al 2003;Metherate 2004) and other cortical areas.…”

“…Cholinergic interneurons in the nucleus accumbens (NAc) can affect GABAergic transmission within the NAc itself via nAChR activation (de Rover et al 2002). In addition, these cholinergic interneurons could be important in lasting changes in microcircuitries that affect animal behavior, because their intrinsic firing properties are altered during behavioral sensitization to amphetamine (de Rover et al 2004). Furthermore, it is known from immunohistochemical data that a small fraction of bipolar interneurons in layer II/III of the sensory and motor cortices are cholinergic (Houser et al 1985).…”

Chronic Nicotine Cell Specifically Upregulates Functional α4* Nicotinic Receptors: Basis for Both Tolerance in Midbrain and Enhanced Long-Term Potentiation in Perforant Path

“…The first is sensitization, both locomotor (Ksir et al, 1985;de Rover et al, 2004) and cognitive (Rezvani and Levin, 2001;Dani and Bertrand, 2007). In the human context, cognitive sensitization is epitomized by smokers' reports that they think better when they smoke; this anecdotal observation is confirmed by data that smokers who smoke nicotine cigarettes (but not nicotine-free cigarettes) display certain cognitive enhancements (Rusted and Warburton, 1992;Rusted et al, 1995).…”

Inhibition of both α7* and β2* nicotinic acetylcholine receptors is necessary to prevent development of sensitization to cocaine-elicited increases in extracellular dopamine levels in the ventral striatum

“…It has been shown that repeated exposures to nicotine enhance behavioral sensitization to amphetamine (de Rover et al 2004), while blockade of nAChRs prevents the induction of behavioral sensitization to amphetamine or cocaine (Schoffelmeer et al 2002).…”