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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 5 to 7 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 5 to 7 days of withdrawal from saline (top) or cocaine (bottom) self-administration. (b) Plot showing the mean number of spikes fired at each current step from LHb neurons 5 to 7 days after cocaine or saline self-administration training (saline/cocaine, n = 18/9; rats = 4/6). (c) Graph showing the mean threshold of action potentials (saline/cocaine, n = 18/19; rats = 4/6). (d) Graph showing the mean membrane resistance of LHb cells (saline/ cocaine, n = 18/19; rats = 4/6). (e) Example of threshold, 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 = 15/13; rats = 4/6) and mAHP (saline/cocaine, n = 14/14; rats = 4/6) measurements relative to spike threshold. *, P < .05, based on ANOVA comparison; **, P < .01 based on t test.
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Figure 6: Lateral habenula (LHb) neuron characteristics 5 to 7 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 5 to 7 days of withdrawal from saline (top) or cocaine (bottom) self-administration. (b) Plot showing the mean number of spikes fired at each current step from LHb neurons 5 to 7 days after cocaine or saline self-administration training (saline/cocaine, n = 18/9; rats = 4/6). (c) Graph showing the mean threshold of action potentials (saline/cocaine, n = 18/19; rats = 4/6). (d) Graph showing the mean membrane resistance of LHb cells (saline/ cocaine, n = 18/19; rats = 4/6). (e) Example of threshold, 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 = 15/13; rats = 4/6) and mAHP (saline/cocaine, n = 14/14; rats = 4/6) measurements relative to spike threshold. *, P < .05, based on ANOVA comparison; **, P < .01 based on t test.

Mentions: After observing that the cocaine-induced increases in membrane excitability and membrane resistance returned to saline-control levels by day 45 of withdrawal, we decided to examine a 5- to 7-day moderate term (MT) withdrawal point to better understand the time course of these observed changes. Again, the same cell characteristics were measured at this MT time point as were measured at the ST and LT withdrawal time points. A 2-way repeated-measures ANOVA using spike number as the dependent variable repeated at each current step for saline MT and cocaine MT treatment groups showed that the cocaine MT treatment had a significant increase in cell excitability (F[1, 35] = 5.39, n = 37, P < .05), similar to the cocaine ST treatment group (Figure 6a, b). Bonferroni's multiple comparisons test was used to check for differences at each current step. This result reveals that LHb neurons maintain increased levels of excitability until at least 7 days after cocaine self-administration training (a Bonferroni posttest comparing withdrawal days 5–7 showed no differences between withdrawal days; P = 1.00 for all comparisons). Measurements of other cellular characteristics including the action potential threshold, fAHP, and mAHP again revealed no significant effects of cocaine at the MT withdrawal point (Figure 6c, e, f). However, the membrane resistance of LHb cells after MT withdrawal from cocaine self-administration was again significantly different from saline controls (Figure 6d; p < .01, n sal/coc = 18/19), further supporting a correlation between membrane excitability and membrane resistance.


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 5 to 7 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 5 to 7 days of withdrawal from saline (top) or cocaine (bottom) self-administration. (b) Plot showing the mean number of spikes fired at each current step from LHb neurons 5 to 7 days after cocaine or saline self-administration training (saline/cocaine, n = 18/9; rats = 4/6). (c) Graph showing the mean threshold of action potentials (saline/cocaine, n = 18/19; rats = 4/6). (d) Graph showing the mean membrane resistance of LHb cells (saline/ cocaine, n = 18/19; rats = 4/6). (e) Example of threshold, 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 = 15/13; rats = 4/6) and mAHP (saline/cocaine, n = 14/14; rats = 4/6) measurements relative to spike threshold. *, P < .05, based on ANOVA comparison; **, P < .01 based on t test.
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Figure 6: Lateral habenula (LHb) neuron characteristics 5 to 7 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 5 to 7 days of withdrawal from saline (top) or cocaine (bottom) self-administration. (b) Plot showing the mean number of spikes fired at each current step from LHb neurons 5 to 7 days after cocaine or saline self-administration training (saline/cocaine, n = 18/9; rats = 4/6). (c) Graph showing the mean threshold of action potentials (saline/cocaine, n = 18/19; rats = 4/6). (d) Graph showing the mean membrane resistance of LHb cells (saline/ cocaine, n = 18/19; rats = 4/6). (e) Example of threshold, 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 = 15/13; rats = 4/6) and mAHP (saline/cocaine, n = 14/14; rats = 4/6) measurements relative to spike threshold. *, P < .05, based on ANOVA comparison; **, P < .01 based on t test.
Mentions: After observing that the cocaine-induced increases in membrane excitability and membrane resistance returned to saline-control levels by day 45 of withdrawal, we decided to examine a 5- to 7-day moderate term (MT) withdrawal point to better understand the time course of these observed changes. Again, the same cell characteristics were measured at this MT time point as were measured at the ST and LT withdrawal time points. A 2-way repeated-measures ANOVA using spike number as the dependent variable repeated at each current step for saline MT and cocaine MT treatment groups showed that the cocaine MT treatment had a significant increase in cell excitability (F[1, 35] = 5.39, n = 37, P < .05), similar to the cocaine ST treatment group (Figure 6a, b). Bonferroni's multiple comparisons test was used to check for differences at each current step. This result reveals that LHb neurons maintain increased levels of excitability until at least 7 days after cocaine self-administration training (a Bonferroni posttest comparing withdrawal days 5–7 showed no differences between withdrawal days; P = 1.00 for all comparisons). Measurements of other cellular characteristics including the action potential threshold, fAHP, and mAHP again revealed no significant effects of cocaine at the MT withdrawal point (Figure 6c, e, f). However, the membrane resistance of LHb cells after MT withdrawal from cocaine self-administration was again significantly different from saline controls (Figure 6d; p < .01, n sal/coc = 18/19), further supporting a correlation between membrane excitability and membrane resistance.

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.

Show MeSH
Related in: MedlinePlus