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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 45 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 45 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 45 days after cocaine or saline self-administration training (saline/cocaine, n = 10/15; rats = 3/3). (c) Graph showing the mean threshold of action potentials (saline/cocaine, n = 10/15; rats = 3/3). (d) Graph showing the mean membrane resistance of LHb cells (saline/cocaine, n = 10/15; rats = 3/3). (e) Example of fAHP and mAHP measurement locations on a typical isolated spike trace. (f) Graph of mean fAHP (saline/cocaine, n = 6/10; rats = 3/3) and mAHP (saline/cocaine, n = 7/12; rats = 3/3) measurements relative to spike threshold.
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Figure 5: Lateral habenula (LHb) neuron characteristics 45 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 45 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 45 days after cocaine or saline self-administration training (saline/cocaine, n = 10/15; rats = 3/3). (c) Graph showing the mean threshold of action potentials (saline/cocaine, n = 10/15; rats = 3/3). (d) Graph showing the mean membrane resistance of LHb cells (saline/cocaine, n = 10/15; rats = 3/3). (e) Example of fAHP and mAHP measurement locations on a typical isolated spike trace. (f) Graph of mean fAHP (saline/cocaine, n = 6/10; rats = 3/3) and mAHP (saline/cocaine, n = 7/12; rats = 3/3) measurements relative to spike threshold.

Mentions: After observing that cocaine self-administration leads to an increase in the membrane excitability of LHb neurons 24 to 48 hours later, we then looked at a more protracted withdrawal time point at 45 days to determine if these changes were persistent. The same cell characteristics measured at 24 to 48 hours of withdrawal were then measured after 45 days of withdrawal. Again, spike numbers at each current step were counted as a measure of the membrane excitability (Figure 5a). Two-way repeated-measures ANOVA using spike number as the dependent variable repeated at each current step for cocaine LT and saline LT treatment groups revealed no significant effect of the treatment on the number of spikes across all current steps (F[1, 23] = 0.17, n = 25, P = .68). Thus, it appears that the initial cocaine-induced increase in membrane excitability returns to baseline levels at some time point after 48 hours of withdrawal (Figure 5b). Additionally, the membrane resistance no longer differed significantly from saline-exposed controls 45 days after the last cocaine exposure (Figure 5d). All other cellular measures including action potential threshold, fAHP, and mAHP also showed no statistical differences between treatment groups after LT withdrawal (Figure 5c, e, f). Taken together, these results indicate that the cocaine-induced increase in LHb cell excitability returns to baseline at some point between 2 and 45 days of withdrawal from cocaine and is correlated with changes in 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 45 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 45 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 45 days after cocaine or saline self-administration training (saline/cocaine, n = 10/15; rats = 3/3). (c) Graph showing the mean threshold of action potentials (saline/cocaine, n = 10/15; rats = 3/3). (d) Graph showing the mean membrane resistance of LHb cells (saline/cocaine, n = 10/15; rats = 3/3). (e) Example of fAHP and mAHP measurement locations on a typical isolated spike trace. (f) Graph of mean fAHP (saline/cocaine, n = 6/10; rats = 3/3) and mAHP (saline/cocaine, n = 7/12; rats = 3/3) measurements relative to spike threshold.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4390528&req=5

Figure 5: Lateral habenula (LHb) neuron characteristics 45 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 45 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 45 days after cocaine or saline self-administration training (saline/cocaine, n = 10/15; rats = 3/3). (c) Graph showing the mean threshold of action potentials (saline/cocaine, n = 10/15; rats = 3/3). (d) Graph showing the mean membrane resistance of LHb cells (saline/cocaine, n = 10/15; rats = 3/3). (e) Example of fAHP and mAHP measurement locations on a typical isolated spike trace. (f) Graph of mean fAHP (saline/cocaine, n = 6/10; rats = 3/3) and mAHP (saline/cocaine, n = 7/12; rats = 3/3) measurements relative to spike threshold.
Mentions: After observing that cocaine self-administration leads to an increase in the membrane excitability of LHb neurons 24 to 48 hours later, we then looked at a more protracted withdrawal time point at 45 days to determine if these changes were persistent. The same cell characteristics measured at 24 to 48 hours of withdrawal were then measured after 45 days of withdrawal. Again, spike numbers at each current step were counted as a measure of the membrane excitability (Figure 5a). Two-way repeated-measures ANOVA using spike number as the dependent variable repeated at each current step for cocaine LT and saline LT treatment groups revealed no significant effect of the treatment on the number of spikes across all current steps (F[1, 23] = 0.17, n = 25, P = .68). Thus, it appears that the initial cocaine-induced increase in membrane excitability returns to baseline levels at some time point after 48 hours of withdrawal (Figure 5b). Additionally, the membrane resistance no longer differed significantly from saline-exposed controls 45 days after the last cocaine exposure (Figure 5d). All other cellular measures including action potential threshold, fAHP, and mAHP also showed no statistical differences between treatment groups after LT withdrawal (Figure 5c, e, f). Taken together, these results indicate that the cocaine-induced increase in LHb cell excitability returns to baseline at some point between 2 and 45 days of withdrawal from cocaine and is correlated with changes in 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