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Increased excitability of lateral habenula neurons in adolescent rats following cocaine self-administration.

Neumann PA, Ishikawa M, Otaka M, Huang YH, Schlüter OM, Dong Y - Int. J. Neuropsychopharmacol. (2014)

Bottom Line: However, the mechanisms of this effect are poorly understood.We found two major relevant neuronal subtypes: burst firing neurons and regular spiking neurons.These results may help to explain how cocaine and other drugs negatively impact affect states.

View Article: PubMed Central - PubMed

Affiliation: Neuroscience Department (Drs Neumann, Ishikawa, Otaka, and Dong), and Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA (Dr Huang); Molecular Neurobiology, European Neuroscience Institute, Göttingen, Germany (Dr Schlüter). pan23@pitt.edu yandong@pitt.edu.

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Lateral habenula (LHb) neuron characteristics 1 to 2 days after cocaine/saline self-administration. (a) Example traces showing typical current steps from −50 to +10 pA (left) and +90 pA (right) in LHb neurons after saline (top) or cocaine (bottom) self-administration. (b) Plot showing the mean number of spikes fired at each current step from LHb neurons 24 to 48 hours after cocaine or saline self-administration training (saline/cocaine, n = 19/19; rats = 6/6). (c) Graph showing the mean threshold of action potentials (saline/cocaine, n = 19/19; rats = 6/6). (d) Graph showing the mean input resistance of LHb cells (saline/cocaine, n = 19/19; rats = 6/6). (e) Example of fast-decaying afterhyperpolarization (fAHP) and medium-duration afterhyperpolarization (mAHP) measurement locations on a typical isolated spike trace. (f) Graph of mean fAHP (saline/cocaine, n = 10/8; rats = 6/6) and mAHP (saline/cocaine, n = 13/15; rats = 6/4) measurements relative to spike threshold. *, P < .05 based on ANOVA comparison in (b) and Ttest in (d).
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Figure 4: Lateral habenula (LHb) neuron characteristics 1 to 2 days after cocaine/saline self-administration. (a) Example traces showing typical current steps from −50 to +10 pA (left) and +90 pA (right) in LHb neurons after saline (top) or cocaine (bottom) self-administration. (b) Plot showing the mean number of spikes fired at each current step from LHb neurons 24 to 48 hours after cocaine or saline self-administration training (saline/cocaine, n = 19/19; rats = 6/6). (c) Graph showing the mean threshold of action potentials (saline/cocaine, n = 19/19; rats = 6/6). (d) Graph showing the mean input resistance of LHb cells (saline/cocaine, n = 19/19; rats = 6/6). (e) Example of fast-decaying afterhyperpolarization (fAHP) and medium-duration afterhyperpolarization (mAHP) measurement locations on a typical isolated spike trace. (f) Graph of mean fAHP (saline/cocaine, n = 10/8; rats = 6/6) and mAHP (saline/cocaine, n = 13/15; rats = 6/4) measurements relative to spike threshold. *, P < .05 based on ANOVA comparison in (b) and Ttest in (d).

Mentions: To examine the impact of cocaine self-administration on the membrane excitability of LHb cells, we elicited action potentials from these neurons using a series of current injection steps (−50 to +90 pA, 10-pA increments) 24-48 hours after the final self-administration training session. Cells that demonstrated BF spiking during depolarization (approximately 15% of cells) were excluded from excitability analysis due to their irregular firing pattern. Spike numbers at each current step were counted as a measure of the membrane excitability (Figure 4a). Two-way repeated measures ANOVA with spike number as the dependent variable repeated at each current step for both saline and cocaine treatment groups revealed that animals from the treatment group had a significant effect on the membrane excitability in LHb cells 24 to 48 hours after the final cocaine exposure when compared to saline-exposed controls (Figure 4b, P < .05, F[1, 36] = 5.62, n = 38). Bonferroni's multiple comparisons test was performed to detect significant differences between treatment groups at each current step.


Increased excitability of lateral habenula neurons in adolescent rats following cocaine self-administration.

Neumann PA, Ishikawa M, Otaka M, Huang YH, Schlüter OM, Dong Y - Int. J. Neuropsychopharmacol. (2014)

Lateral habenula (LHb) neuron characteristics 1 to 2 days after cocaine/saline self-administration. (a) Example traces showing typical current steps from −50 to +10 pA (left) and +90 pA (right) in LHb neurons after saline (top) or cocaine (bottom) self-administration. (b) Plot showing the mean number of spikes fired at each current step from LHb neurons 24 to 48 hours after cocaine or saline self-administration training (saline/cocaine, n = 19/19; rats = 6/6). (c) Graph showing the mean threshold of action potentials (saline/cocaine, n = 19/19; rats = 6/6). (d) Graph showing the mean input resistance of LHb cells (saline/cocaine, n = 19/19; rats = 6/6). (e) Example of fast-decaying afterhyperpolarization (fAHP) and medium-duration afterhyperpolarization (mAHP) measurement locations on a typical isolated spike trace. (f) Graph of mean fAHP (saline/cocaine, n = 10/8; rats = 6/6) and mAHP (saline/cocaine, n = 13/15; rats = 6/4) measurements relative to spike threshold. *, P < .05 based on ANOVA comparison in (b) and Ttest in (d).
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Figure 4: Lateral habenula (LHb) neuron characteristics 1 to 2 days after cocaine/saline self-administration. (a) Example traces showing typical current steps from −50 to +10 pA (left) and +90 pA (right) in LHb neurons after saline (top) or cocaine (bottom) self-administration. (b) Plot showing the mean number of spikes fired at each current step from LHb neurons 24 to 48 hours after cocaine or saline self-administration training (saline/cocaine, n = 19/19; rats = 6/6). (c) Graph showing the mean threshold of action potentials (saline/cocaine, n = 19/19; rats = 6/6). (d) Graph showing the mean input resistance of LHb cells (saline/cocaine, n = 19/19; rats = 6/6). (e) Example of fast-decaying afterhyperpolarization (fAHP) and medium-duration afterhyperpolarization (mAHP) measurement locations on a typical isolated spike trace. (f) Graph of mean fAHP (saline/cocaine, n = 10/8; rats = 6/6) and mAHP (saline/cocaine, n = 13/15; rats = 6/4) measurements relative to spike threshold. *, P < .05 based on ANOVA comparison in (b) and Ttest in (d).
Mentions: To examine the impact of cocaine self-administration on the membrane excitability of LHb cells, we elicited action potentials from these neurons using a series of current injection steps (−50 to +90 pA, 10-pA increments) 24-48 hours after the final self-administration training session. Cells that demonstrated BF spiking during depolarization (approximately 15% of cells) were excluded from excitability analysis due to their irregular firing pattern. Spike numbers at each current step were counted as a measure of the membrane excitability (Figure 4a). Two-way repeated measures ANOVA with spike number as the dependent variable repeated at each current step for both saline and cocaine treatment groups revealed that animals from the treatment group had a significant effect on the membrane excitability in LHb cells 24 to 48 hours after the final cocaine exposure when compared to saline-exposed controls (Figure 4b, P < .05, F[1, 36] = 5.62, n = 38). Bonferroni's multiple comparisons test was performed to detect significant differences between treatment groups at each current step.

Bottom Line: However, the mechanisms of this effect are poorly understood.We found two major relevant neuronal subtypes: burst firing neurons and regular spiking neurons.These results may help to explain how cocaine and other drugs negatively impact affect states.

View Article: PubMed Central - PubMed

Affiliation: Neuroscience Department (Drs Neumann, Ishikawa, Otaka, and Dong), and Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA (Dr Huang); Molecular Neurobiology, European Neuroscience Institute, Göttingen, Germany (Dr Schlüter). pan23@pitt.edu yandong@pitt.edu.

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Related in: MedlinePlus