Figure 4.
Changes in conditional multireceptive (CMR) neuronal responses induced by CNS depressant drugs. Neuronal responses in the ventrolateral periaqueductal gray (PAG) and lateral amygdala (LA) are depressed by low doses of depressant drugs. Low doses of barbiturates (which enhance GABAA receptor activity) or ketamine (uncompetitive NMDA receptor antagonist) reduce CMR extracellular action potential responses to external stimuli. Panel A shows the mean (± SEM) reduction of both spontaneous (Spont.) and thermally evoked PAG neuronal firing by pentobarbital (N = 18 neurons) 15 minutes after systemic administration with recovery by 30 minutes. Panel B shows examples of rate meter histogram analysis of a PAG spontaneous and evoked neuronal firing in response to a single 30-second (bracket) noxious thermal stimulation (53°C) before (Control column), 15 minutes after pentobarbital (15 mg/kg i.p.) treatment (Drug column), and subsequent recovery (at 30 minutes) (Recovery column). Prior to pentobarbital the majority (18/35) of PAG neurons increased firing in response to the thermal stimulus in this study. (Note 10 mg/kg of pentobarbital had no significant effect on PAG neuronal firing, whereas 20 mg/kg produced greater depression of PAG firing than the 15 mg dose.) The action potential above the top histogram represents the waveform of the neuron being analyzed. The onset and duration of the thermal stimulus is illustrated by the bracket. *Significance at P < 0.01 (repeated-measures ANOVA). Panel C shows a representative example of the poststimulus time histogram (PSTH) analysis of the action of an uncompetitive NMDA antagonist (ketamine) to reversibly block the sensory responsiveness of LA neurons. In the control column the LA neuron exhibited an onset response to the auditory stimulus before ketamine treatment. LA neuronal firing was significantly reduced (P < .01, paired t-test) and almost completely suppressed 15 minutes after ketamine (30 mg/kg i.p.) treatment (drug column). Four hours after ketamine treatment, the LA neuronal response was comparable tothat prior to ketamine treatment (recovery column). The inset the control column in line C shows an example of the digital oscilloscope tracings for the PSTH. Action potential amplitude in C: 300 μV. N = number of action potentials in the PSTH. Treatment was given in unanesthetized awake, behaving rats with microwire recording electrode. (Acoustic stimulus parameters: 12 kHz tone burst, 100 ms duration, 5 ms rise-fall, 100 dB SPL, 0.5 Hz rate) (PSTH parameters 50 stimulus presentations, 1 ms bin width). All data were taken from awake, behaving rats. The data in line C is representative of the change in the mean number of action potentials/PSTH (control mean = 182.1 ± 42.0 [SEM] vs. 9.6 ± 2.0 drug mean). Note: Both drug doses were less than 30% of the anesthetic dose. (A, B: modified from Faingold and others 2014b; C: modified from Faingold 2014b).