Figure 1.
Analysis of the firing frequency of CA1 pyramidal cells from Tat– or Tat+ mice treated with vehicle or morphine time-release implants in which morphine is present (500 nm) or withheld (0 nm) during the recordings. A, B, Representative traces are depicted at the 100- and 350-pA current steps in which morphine (Morph) is present (500 nm; A) or withheld (0 nm; B) during the recordings. A, C, Pyramidal cell firing rates were unaffected by sustained morphine exposure. B, D, By contrast, when morphine was withheld during recordings from mice previously maintained on morphine, firing rates were significantly suppressed. C, CA1 pyramidal cells from Tat+ mice fired at a lower frequency than those of Tat− mice between 50 and 150 pA, but were unaffected by exposure to morphine during recordings (C). C, D, Tat genotype interacted with the amount of current applied. D, Withholding morphine from slices isolated from morphine-exposed mice resulted in significantly lower pyramidal cell firing rates at stimulating currents from 275 to 375 pA compared with morphine-naive cells (†p < 0.05); nevertheless, Tat and morphine did not interact statistically perhaps because the effect of withholding morphine was not seen at other stimulating currents and at 25- to 200-pA current steps in pyramidal cells from Tat+ mice had lower firing rates than those from Tat− mice. E, Resting membrane potential (VR) showed significant interactions when exposed to Tat or morphine. Tat+ neurons were significantly more depolarized at rest, while morphine treatment appeared to negate the effects of Tat. F, While no significant effects were noted in rheobase, there was a trend (p = 0.06) for pyramidal cells from Tat+ mice to require a greater amount of current to reach a threshold for firing compared with cells from Tat− mice. G, The threshold for firing (mV) is significantly reduced in cells from morphine-treated mice. H, There was a significant interaction between Tat and morphine on resting membrane potential (VR), which resulted from greater depolarized membrane potentials in vehicle-treated Tat+ mice. I, Tat significantly increased rheobase, regardless of prior morphine treatment during the recording of morphine-withheld slices. Pyramidal cells from Tat+ mice required a greater amount of current (pA) to reach the threshold potential for firing than Tat− mice, although the firing threshold (mV) of CA1 pyramidal cells was unaffected by Tat or morphine exposure (J). Patched cells were stimulated with 500-ms current pulses starting at −100 pA and escalating to 400 pA in 25-pA steps; * indicates significant difference between Tat− and Tat+ tissues; † indicates a significant decline in firing rates in slices from Tat+, but not Tat−, mice previously exposed to morphine when morphine was withheld (p < 0.05).