Arousal and drug abuse

Abstract

The reticular activating system (RAS) is not an amorphous region but distinct nuclei with specific membrane properties that dictate their firing during waking and sleep. The locus coeruleus and raphe nucleus fire during waking and slow wave sleep, with the pedunculopontine nucleus (PPN) firing during both waking and REM sleep, the states manifesting arousal-related EEG activity. Two important discoveries in the PPN in the last 10 years are, 1) that some PPN cells are electrically coupled, and 2) every PPN cell manifests high threshold calcium channels that allow them to oscillate at beta/gamma band frequencies. The role of arousal in drug abuse is considered here in terms of the effects of drugs of abuse on these two mechanisms. Drug abuse and the perception of withdrawal/relapse are mediated by neurobiological processes that occur only when we are awake, not when we are asleep. These relationships focus on the potential role of arousal, more specifically of RAS electrical coupling and gamma band activity, in the addictive process as well as the relapse to drug use.

Keywords: Cocaine; Connexin 36; Dopamine; Modafinil; N- and P/Q-type calcium channels; Preconscious awareness.

Figure 1. Distribution of PPN neurons according to electrophysiological type (I, II, or III) and high threshold calcium channel type (N+P/Q, N only, P/Q only)

Left side. Graph of the distribution of cells by cell type (Type I red, Type II blue, Type III green columns) and by channel type (N only, P/Q only, N+P/Q). Note that the numbers in each column are cell counts of recorded cells, and the percentage of cell type or channel type are in brackets in the axis legends. Right side. Pie chart of the percentage of cells by cell type and channel type. Note that the numbers inside the chart represent percent, not cell counts. Basically, the sample of almost 200 PPN cells shows that all cell types manifest all three types of channel expression. Since Type I cells are non-cholinergic, Type II cells are 2/3 cholinergic, and Type III cells are 1/3 cholinergic, it is highly likely that all three transmitter types (cholinergic, glutamatergic, and GABAergic) manifest all three channel types.