Nicotine and food induced dopamine release in the nucleus accumbens of the rat: Putative role of α7 nicotinic receptors in the ventral tegmental area

Schilström, Björn; Svensson, Hanna; Svensson, Torgny H.; Nomikos, George G.

doi:10.1016/s0306-4522(98)00114-6

Cited by 186 publications

(128 citation statements)

References 29 publications

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“…Although little is known on the effects of SSR180711 on mesolimbic DA dynamics (Hansen et al, 2007), it seems unlikely that this agent would directly block NAC DA increase, given the well known action of nicotine to increase DA release in the NAC (Wonnacott et al, 2005), an effect blocked by a7 antagonists (Schilstrom et al, 1998(Schilstrom et al, , 2000. The capacity of SSR180711 to increase glutamate neurotransmission in the hippocampus as well as increase dopamine levels in the PFC (Biton et al, 2007;Pichat et al, 2007) could underlie reversal of amphetamine-induced disruption and potentiation of LI, since both would be expected to reduce mesolimbic DA function and block behavioral effects of amphetamine Grace, 2005, 2007;Grace, 1991;Jackson and Moghaddam, 2001).…”

Section: Reversal Of Disrupted Li: Putative Efficacy For Positive Symmentioning

confidence: 99%

Pro-Cognitive and Antipsychotic Efficacy of the α7 Nicotinic Partial Agonist SSR180711 in Pharmacological and Neurodevelopmental Latent Inhibition Models of Schizophrenia

Barak

Arad

Levie

et al. 2009

Neuropsychopharmacol

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Schizophrenia symptoms can be segregated into positive, negative and cognitive, which exhibit differential sensitivity to drug treatments. Accumulating evidence points to efficacy of a7 nicotinic receptor (nAChR) agonists for cognitive deficits in schizophrenia but their activity against positive symptoms is thought to be minimal. The present study examined potential pro-cognitive and antipsychotic activity of the novel selective a7 nAChR partial agonist SSR180711 using the latent inhibition (LI) model. LI is the reduced efficacy of a previously nonreinforced stimulus to gain behavioral control when paired with reinforcement, compared with a novel stimulus. Here, no-drug controls displayed LI if non-reinforced pre-exposure to a tone was followed by weak but not strong conditioning (2 vs 5 tone-shock pairings). MK801 (0.05 mg/kg, i.p.) -treated rats as well as rats neonatally treated with nitric oxide synthase inhibitor L-NoArg (10 mg/kg, s.c.) on postnatal days 4-5, persisted in displaying LI with strong conditioning, whereas amphetamine (1 mg/kg) -treated rats failed to show LI with weak conditioning. SSR180711 (0.3, 1, 3 mg/kg, i.p.) was able to alleviate abnormally persistent LI produced by acute MK801 and neonatal L-NoArg; these models are believed to model cognitive aspects of schizophrenia and activity here was consistent with previous findings with a7-nAChR agonists. In addition, unexpectedly, SSR180711 (1, 3 mg/kg, i.p.) potentiated LI with strong conditioning in nodrug controls and reversed amphetamine-induced LI disruption, two effects considered predictive of activity against positive symptoms of schizophrenia. These findings suggest that SSR180711 may be beneficial not only for the treatment of cognitive symptoms in schizophrenia, as reported multiple times previously, but also positive symptoms.

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Section: Reversal Of Disrupted Li: Putative Efficacy For Positive Symmentioning

confidence: 99%

Pro-Cognitive and Antipsychotic Efficacy of the α7 Nicotinic Partial Agonist SSR180711 in Pharmacological and Neurodevelopmental Latent Inhibition Models of Schizophrenia

Barak

Arad

Levie

et al. 2009

Neuropsychopharmacol

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“…Despite the widespread expression of nAChRs throughout the brain, the nAChRs found in VTA are critically important in the rewarding effects of nicotine (Schilstrom et al, 1998b;Nisell et al, 1994). When the nAChR antagonist mecamylamine (MEC) is focally infused in the VTA through a microdialysis probe, the increase in extracellular DA in the NAcc caused by a systemic injection of nicotine is blocked.…”

Section: Vta Nachrs and Behaviormentioning

confidence: 99%

“…These nAChRs are sensitive to MLA, a selective inhibitor of nAChRs that contain the ␣7 subunit (Alkondon and Albuquerque, 1993;Seguela et al, 1993). In vivo focal injection of MLA into the VTA also prevents nicotine-induced increases in accumbal DA release (Schilstrom et al, 1998b). Nicotinic AChRs consisting of ␣7 subunits are well-suited for modulating synaptic transmission as they have a high calcium permeability, and this calcium flux occurs at resting membrane potentials when activated by agonists (Seguela et al, 1993;.…”

Section: Vta Nachrs and Behaviormentioning

confidence: 99%

“…Following activation, even with nicotine concentrations as low as 100 -500 nM, the somatic nAChRs desensitize within minutes (Pidoplichko et al, 1997;Fisher et al, 1998;. However, at the same time, in vivo biochemical studies show that a single systemic injection of nicotine enhances DA release in the NAcc for more than an hour (Di Chiara and Imperato, 1988;Di Chiara, 2000;Imperato et al, 1986;Schilstrom et al, 1998a;Schilstrom et al, 1998b). Clearly, there must be additional mechanisms that follow nAChR activation, which induce the long-term enhancement of DA release.…”

Section: Vta Nachrs and Behaviormentioning

confidence: 99%

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Cellular and synaptic mechanisms of nicotine addiction

2002

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ABSTRACT:The tragic health effects of nicotine addiction highlight the importance of investigating the cellular mechanisms of this complex behavioral phenomenon. The chain of cause and effect of nicotine addiction starts with the interaction of this tobacco alkaloid with nicotinic acetylcholine receptors (nAChRs). This interaction leads to activation of reward centers in the CNS, including the mesoaccumbens DA system, which ultimately leads to behavioral reinforcement and addiction. Recent findings from a number of laboratories have provided new insights into the biologic processes that contribute to nicotine self-administration.Examination of the nAChR subtypes expressed within the reward centers has identified potential roles for these receptors in normal physiology, as well as the effects of nicotine exposure. The high nicotine sensitivity of some nAChR subtypes leads to rapid activation followed in many cases by rapid desensitization. Assessing the relative importance of these molecular phenomena in the behavioral effects of nicotine presents an exciting challenge for future research efforts.

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“…Because of their high permeability to calcium (Seguela et al, 1993), it is likely that α7 nAChRs modulate the release of many neurotransmitters at a variety of synapses. Activation of α7 nAChRs can modulate the release of GABA (Alkondon et al, 1997;Wanaverbecq et al, 2007), glutamate (Gray et al, 1996;McGehee et al, 1995), dopamine (Schilstrom et al, 1998), and noradrenaline (Li et al, 1998). Also, it has been shown that α7 nAChRs regulate the excitability of CA1 pyramidal cells (Dani, 2000) and dentate granule cells (Frazier et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Modulation of spontaneous hippocampal synaptic events with 5-hydroxyindole, 4OH-GTS-21, and rAAV-mediated α7 nicotinic receptor gene transfer

et al. 2008

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One approach to treatment of negative cognitive effects associated with Alzheimer's disease and schizophrenia may involve activation of neuronal α7 nicotinic acetylcholine receptors (nAChRs). We used the α7-selective partial agonist 3-(4-hydroxy, 2-methoxy-benzylidene)anabaseine (4OH-GTS-21), the α7 modulator 5-hydroxyindole (5-HI), and recombinant adeno-associated virus (rAAV)-mediated α7 gene transfer in order to test the hypothesis whether combining these strategies would significantly increase indirect measures of α7 nAChR function, including measures of spontaneous synaptic events in CA1 pyramidal cells. 5-HI (1mM), and 5-HI (1 mM) + 4OH-GTS-21 (5 μM) increased the frequency of APV-and NBQX-sensitive currents, while 5-HI + 4OH-GTS-21 increased the frequency and amplitude of bicuculline-sensitive currents. Effects on EPSCs were blocked with tetrodotoxin (TTX) (1 μM), but not by methyllycaconitine (MLA) (50 nM). Neither TTX nor MLA reduced the potentiation of IPSC frequencies. However, TTX blocked, and in some cases MLA reduced, the potentiation of IPSC amplitudes. These data suggest that effects of 5-HI + 4OH-GTS-21 on EPSC frequency were associated with action potential-dependent transmitter release produced by 5HI, and that potentiation of IPSC amplitudes resulted at least in part, from activation of α7 nAChRs. Finally, rAAV-mediated α7 gene transfer did not alter the magnitude of effects produced by 5-HI or 5-HI + 4OH-GTS-21. Thus, although we previously showed direct measures of α7 nAChR function were enhanced by α7 gene transfer, indirect measures of α7 nAChRs function were not significantly enhanced by combining α7 gene transfer with either agonist activation or positive allosteric modulation of α7 nAChRs.

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Nicotine and food induced dopamine release in the nucleus accumbens of the rat: Putative role of α7 nicotinic receptors in the ventral tegmental area

Cited by 186 publications

References 29 publications

Pro-Cognitive and Antipsychotic Efficacy of the α7 Nicotinic Partial Agonist SSR180711 in Pharmacological and Neurodevelopmental Latent Inhibition Models of Schizophrenia

Pro-Cognitive and Antipsychotic Efficacy of the α7 Nicotinic Partial Agonist SSR180711 in Pharmacological and Neurodevelopmental Latent Inhibition Models of Schizophrenia

Cellular and synaptic mechanisms of nicotine addiction

Modulation of spontaneous hippocampal synaptic events with 5-hydroxyindole, 4OH-GTS-21, and rAAV-mediated α7 nicotinic receptor gene transfer

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