Addictive neurons

Abstract

Since the reward center is considered to be the area tegmentalis ventralis of the hypothalamus, logically its neurons could mainly be responsible for addiction. However, the literature asserts that almost any neurons of CNS can respond to one or another addictive compound. Obviously not only addictive nicotine, but also alcohol, amphetamine, cannabis, cocaine, heroin and morphine may influence dopaminergic cells alone in VTA. Moreover, paradoxically some of these drugs ameliorate symptoms, counterbalance syndromes, cure diseases and improve health, not only those related to the CNS and in adults, but also almost all other organs and in children, e.g. epilepsy.

Keywords: ADP; AHP; LTD; LTP; amygdala; lateral septum; medial prefrontal cortex; paired pulse facilitation; rebound action potential; spike.

Figure 1. VTA of rhesus monkey Macaca mulatta

Both hemispheres of the brain are shown in horizontal plane (www.brainmaps.org). Note that this sectioning enables inclusion of more nuclei in a single slice than the coronal one (see Figure 2). Specifically, also the C – cerebellum is present. Reprinted with permission ^[123].

Figure 2. VTA of mouse Mus Musculus

Coronal section of the brain containing several regions including H – hippocampus. VTA is shown at higher magnification (www.brainmaps.org). Reprinted with permission ^[123].

Figure 3. Spontaneous bursting

(A) Single spike and bursts in rat VTA DA in vivo ^[24]. There is an adaptation of amplitude during the bursts, but note that the same is not always observed at opposite phases of spikes. (B) Spiking in rat LS neuron in whole-cell mode after nicotine in vitro. Amplitudes at overshoot are similar but there is a decrease at negative potential and it concerns the AHP as elucidated earlier. Reprinted with permission ^[20].

Figure 4. Sag and RAP

Properties of MP and APs are different in LS, SNc and VTA neurons. LS neuron is silent at RMP ^[19] while cells in SNc and VTA are spontaneously active as can be appreciated by APs prior to hyperpolarizing steps. Note the progressive increase in sag (despite lesser current magnitude of −200 vs. 300 pA) and latency to 1^st RAP (see also the text). The AHP in SNc is of highest amplitude at 1^st RAP and gradually decreases thereafter while in LS and VTA it is relatively constant. Dashed lines closely reflect the RMP with values of −59 mV in LS and an equal −50 mV in SNc and VTA. Reprinted with permission ^[30].

Figure 5. Comparison of I_h in the brain

(A) Inward currents in rat LS neuron before and after 10 μM ZD 7288 ^[19]. Note the obliteration of tail current. (B) Currents waveform in VTA DA neurons from rats treated with saline (Control) and sensitized to cocaine. The I_h in VTA are more pronounced and activate faster than in LS. Cocaine influences only the peak tail currents. This is expected, since ZD completely blocked the I_h in LS, while cocaine only decreased it significantly in VTA. Furthermore, currents in the presence of cocaine still resemble the I_h but after ZD there is no a sag counterpart. Occasional PSC – postsynaptic current (♪) validates both the cell and slice qualities. Pulse durations are identical at 1 s and the respective amplitude scales are 120 and 200 pA. Reprinted with permission ^[92].