Talk:Cognitive euphoria

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Neurological Analysis

Electrodes can reliably induce euphoria when stimulating the nucleus accumbens

"Recent studies on deep brain stimulation (DBS) of the nucleus accumbens (NA)—a center of the brain well known to mediate reward, pleasure, and addiction—have provided proof of principle evidence that DBS might be able to induce euphoria in a rapid, well-modulated manner, with potentially much higher efficacy than previous neuropsychiatric interventions"

"These examples of euphoria—inducible in a rapid and very titratable fashion by a simple linear increase of DBS voltage—certainly provide an only preliminary empirical basis for further ethical discussion. More studies in larger patient groups are required to confirm these effects and study their nature in more detail. Nevertheless, at least in principle, an effect of euphoria induced by NA DBS seems highly plausible based on the fact that the NA is a critical center for the experience of reward and pleasure: Increases in NA neuron activity and dopamine release are observed during expectations and experience of rewards (Adinoff, 2004; de la Fuente-Fernandez et al. 2002; Doyon et al. 2005; Schultz, 2004), and neuroimaging studies have shown increases in ventral striatal activity associated with euphoric responses to dextroamphetamine (Drevets et al. 2001), cocaine-induced euphoria (Breiter et al. 1997), monetary reward (Cohen et al. 2005; Knutson et al. 2001), pleasurable responses to music (Blood and Zatorre 2001), and viewing attractive faces (Aharon et al. 2001)."[1]

Enkephalin, Noradrenaline, and Dopamine systems work in tandem to mediate euphoria

"These results suggest that central grey self-stimulation may depend on the activation of both noradrenaline-containing and enkephalin-containing neurones (sic); indeed, since all of the enkephalin-rich self-stimulation sites referred to above are also rich in catecholamines(17), it is possible that the reward process may generally be regulated by the interaction of noradrenaline, dopamine, and enkephalin systems. Studies on intravenous self-administration of opiate drugs similarly suggest that catecholamine mechanisms are involved in opiate reinforcement(19,20)."[2]

Glutamatergic systems interplay with dopaminergic

"In contrast, ketamine and amphetamine produced additive effects on euphoria and thought disorder"

"Outcome measures where ketamine and amphetamine produce additive effects may be related to the regulation of striatal dopaminergic stimulation, where ketamine has been shown to increase the impact of amphetamine on dopamine release in humans, although ketamine may not stimulate striatal dopamine release by itself.61,71 If the thought-disordering and euphoric effects of ketamine are mediated by striatal dopamine systems, then it is likely that non-D2 dopamine receptors mediate these effects because, with the possible exception of concrete ideation, they do not seem to be blocked by the dopamine D2⁄3 receptor antagonist haloperidol.66 Similarly, dizocilpine (MK-801) self-administration into the nucleus accumbens in animals was not blocked by sulpiride microinjections into this brain region at doses that blocked the self-administration of dopamine transporter antagonists.72"

"Amphetamine and ketamine produced euphoria and emotional distress, predominantly tension or anxiety. However, the amphetamine euphoria was associated with psychomotor activation and hostility, whereas that of ketamine was associated with sedation. This distinction may be relevant to the behavioral effects of alcohol, where dopamine may contribute to the stimulant-related “high” associated with the ascending blood alcohol levels, and blockade of NMDA receptors may contribute to the sedative effects associated with high levels of alcohol consumption and descending blood alcohol levels.46,47 In summary, the present data suggest that despite some overlap, ketamine and amphetamine produce distinct profiles of cognitive and behavioral effects."[3]

Acute ethanol administration correlates euphoria with alpha band brainwaves

"Alpha power was significantly increased by high dose ethanol at 15, 30 and 45 min after drinking while the low dose ethanol did not alter alpha power. Alpha power declined to control levels by 45 min after subjects had finished consuming high-dose ethanol. The incidence of euphoria episodes paralleled this bimodal change in alpha power (y=0.49x+5.61; r~=0.89) and was highly correlated (r=0.95). Only a single short episode of euphoria was reported by one subject who had received low dose ethanol. While the absolute plasma ethanol levels after both doses were not significantly different up to 45 min after drinking began, the slopes were significantly different during the 25-50 min period when the greatest incidence of reported euphoria occurred. The slopes and 95% confidence intervals for high dose- and low dose-induced plasma ethanol curves were 0.599 (0.432-0.767) and 0.153 (0.091-0.214) mg/dl/min"

"Previous studies have demonstrated that ethanol produces increased alpha activity and a slowing of the alpha frequency [9, 10, 13]."[4]

Neuropathological implications of depression in reward-based behaviors

"This symptom cluster appears to be phenomenologically related to the putative functions of the mesolimbic dopaminergic projections from the VTA into the ventral mPFC, amygdala, and ventral striatum [83,84]. These projections are thought to subserve a ‘reward-related system’ that mediates hedonia, motivation, behavioral reinforcement and psychomotor activity [85–88]. For example, dopamine (DA) release into the ventral striatum appears critical for the reinforcing properties of cocaine in rats [89,90], and is very tightly correlated with the euphoric response to dextroamphetamine in humans [91]. The temporal relationships between exposure to natural rewards, DA neuronal firing activity, and extracellular DA concentrations suggest that ventral striatal DA release is involved in forming associations between salient contextual stimuli and internal rewarding events [88,92]. The DA signal may also participate in regulating the timing of behavioral selection by facilitating switching between behaviors and attentional/cognitive sets as reinforcement contingencies change [93,94]. Mesolimbic DA release also modulates afferent synaptic transmission from non-dopaminergic projections into the ventral striatum, PFC, amygdala, hypothalamus, and other limbic structures that may play more critical roles in maintaining behavioral reinforcement [53••,78,83,88].

The anhedonia, amotivation and psychomotor slowing of depression, and the euphoria, hypermotivational state and psychomotor restlessness of mania, have led to the hypothesis that mesolimbic DA function is decreased and increased, respectively, in the depressed and manic phases of BD [83,84,95]. This hypothesis is corroborated by pharmacological evidence and cerebrospinal fluid (CSF) DA metabolite concentrations [95,96]. Anhedonia is also evident in depressive syndromes arising secondary to conditions such as Parkinson’s disease or cocaine abstinence (in cocaine-dependent individuals) that are putatively associated with deficits of DA function [83,97].

In primary MDD and BD, some of the cortical and subcortical targets of the mesolimbic DA system have reduced grey matter volume and cellular abnormalities. The volume of the caudate and nucleus accumbens area is abnormally decreased in MRI and post mortem studies of MDD [98,99]. The amygdala and subgenual PFC have reductions in grey matter and glial cells, with no equivalent reduction in neurons (implying that a decrement in neuropil accounts for the volumetric reduction; for a review, see [3]). These histopathological changes may conceivably interfere with the neurotransmission related to reward processing.

In addition, projections from the ventral mPFC into the VTA [66,74] have been shown to modulate the electrophysiological responses of VTA DA neurons, suggesting another mechanism through which the abnormalities of structure and function in the subgenual PFC may alter reward-related processing. In rats, electrical or glutamatergic stimulation of mPFC areas that include prelimbic cortex elicits burst firing patterns from DA cells in the VTA and increases DA release in the nucleus accumbens [100,101]. These phasic, burst firing patterns of DA neurons are thought to encode information relating to stimuli that predict reward and to deviations between such predictions and the actual occurrence of reward [92]. The hypo- and hypermetabolism found in the subgenual PFC in the depressed and manic phases of BD, respectively, thus suggest the hypothesis that stimulation of VTA neurons by subgenual PFC neurons is correspondingly diminished and facilitated, respectively, in depression and mania [76]. Such functional changes could conceivably be clinically manifested by the hedonic misperceptions and altered motivational states that characterize mood disorders."[5]


  1. Synofzik, M., Schlaepfer, T. E., & Fins, J. J. (2012). How happy is too happy? Euphoria, neuroethics, and deep brain stimulation of the nucleus accumbens. AJOB Neuroscience, 3(1), 30-36.
  2. Belluzzi, J. D., & Stein, L. (1977). Enkephalin may mediate euphoria and drive-reduction reward. Nature, 266(5602), 556.
  3. Krystal, J. H., Perry, E. B., Gueorguieva, R., Belger, A., Madonick, S. H., Abi-Dargham, A., ... & D’Souza, D. C. (2005). Comparative and interactive human psychopharmacologic effects of ketamine and amphetamine: implications for glutamatergic and dopaminergic model psychoses and cognitive function. Archives of general psychiatry, 62(9), 985-995.
  4. Lukas, S. E., Mendelson, J. H., Benedikt, R. A., & Jones, B. (1986). EEG alpha activity increases during transient episodes of ethanol-induced euphoria. Pharmacology Biochemistry and Behavior, 25(4), 889-895.
  5. Drevets, W. C. (2001). Neuroimaging and neuropathological studies of depression: implications for the cognitive-emotional features of mood disorders. Current opinion in neurobiology, 11(2), 240-249.