Heterogeneity of Reward Mechanisms

Abstract

The finding that many drugs that have abuse potential and other natural stimuli such as food or sexual activity cause similar chemical changes in the brain, an increase in extracellular dopamine (DA) in the shell of the nucleus accumbens (NAccS), indicated some time ago that the reward mechanism is at least very similar for all stimuli and that the mechanism is relatively simple. The presently available information shows that the mechanisms involved are more complex and have multiple elements. Multiple brain regions, multiple receptors, multiple distinct neurons, multiple transmitters, multiple transporters, circuits, peptides, proteins, metabolism of transmitters, and phosphorylation, all participate in reward mechanisms. The system is variable, is changed during development, is sex-dependent, and is influenced by genetic differences. Not all of the elements participate in the reward of all stimuli. Different set of mechanisms are involved in the reward of different drugs of abuse, yet different mechanisms in the reward of natural stimuli such as food or sexual activity; thus there are different systems that distinguish different stimuli. Separate functions of the reward system such as anticipation, evaluation, consummation and identification; all contain function-specific elements. The level of the stimulus also influences the participation of the elements of the reward system, there are possible reactions to even below threshold stimuli, and excessive stimuli can change reward to aversion involving parts of the system. Learning and memory of past reward is an important integral element of reward and addictive behavior. Many of the reward elements are altered by repeated or chronic stimuli, and chronic exposure to one drug is likely to alter the response to another stimulus. To evaluate and identify the reward stimulus thus requires heterogeneity of the reward components in the brain.

Female adolescent exposure to cannabinoids causes transgenerational effects on morphine sensitization in female offspring in the absence of in utero exposure

“…The lack of differences between the WIN-F1 and VEH-F1 females with regard to post-synaptic dopamine receptors is consistent with the similarities in Fos induction observed in these two groups. Indeed, previous findings indicate that Fos protein induction in the nucleus accumbens is dopamine dependent (Cousijn et al, 2012; Lajtha and Sershen, 2010). Together, these data suggest that modification in postsynaptic dopamine systems are unlikely to be critical mediators of the differential effects observed in WIN F1 females.…”

“…Another member of the Fos family of immediate early gene transcription factors, cFos, is a classical marker for neuronal activity. Morphine is known to increase the expression of cFos within the nucleus accumbens (Lajtha and Sershen, 2010). Consistent with this finding, we found a trend towards increased cFos in the nucleus accumbens in animals that received a sensitizing regimen of morphine.…”

Unpredictable saccharin reinforcement enhances locomotor responding to amphetamine

“…Electrophysiological recordings of NAcc neurons obtained during operant responding for water/food or cocaine have demonstrated non-overlapping firing patterns, however, suggesting that separate neural circuits are nonetheless recruited during reinforced responding for drugs and natural rewards [39–41]. In addition, similar to how different abused drugs have various pharmacological actions, different natural rewards, such as food and sex, also may have different neurobiological substrates [42, 43]. Furthermore, the magnitude of effects and incentive salience of drugs and natural rewards may be different, with drugs often hijacking natural reward processing systems, leading to exaggerated responses.…”

Sex and Gender in Adverse Drug Events, Addiction, and Placebo

“…Estrogens induce functional changes in dopamine terminals and in GABAergic neurons (Ceylan-Isik et al 2010;Lajtha and Sershen 2010) being this last also influenced by progesterone-derived molecule (Quinones-Jenab and Jenab 2010). Indeed, the use of progesterone as a therapeutic agent has been proposed especially in nicotine and cocaine female users (Lynch and Sofuoglu 2010;Quinones-Jenab and Jenab 2010).…”