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Behavioral functions of the mesolimbic dopaminergic system: an affective neuroethological perspective - PubMed

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Behavioral functions of the mesolimbic dopaminergic system: an affective neuroethological perspective

Antonio Alcaro et al. Brain Res Rev. 2007 Dec.

Abstract

The mesolimbic dopaminergic (ML-DA) system has been recognized for its central role in motivated behaviors, various types of reward, and, more recently, in cognitive processes. Functional theories have emphasized DA's involvement in the orchestration of goal-directed behaviors and in the promotion and reinforcement of learning. The affective neuroethological perspective presented here views the ML-DA system in terms of its ability to activate an instinctual emotional appetitive state (SEEKING) evolved to induce organisms to search for all varieties of life-supporting stimuli and to avoid harms. A description of the anatomical framework in which the ML system is embedded is followed by the argument that the SEEKING disposition emerges through functional integration of ventral basal ganglia (BG) into thalamocortical activities. Filtering cortical and limbic input that spreads into BG, DA transmission promotes the "release" of neural activity patterns that induce active SEEKING behaviors when expressed at the motor level. Reverberation of these patterns constitutes a neurodynamic process for the inclusion of cognitive and perceptual representations within the extended networks of the SEEKING urge. In this way, the SEEKING disposition influences attention, incentive salience, associative learning, and anticipatory predictions. In our view, the rewarding properties of drugs of abuse are, in part, caused by the activation of the SEEKING disposition, ranging from appetitive drive to persistent craving depending on the intensity of the affect. The implications of such a view for understanding addiction are considered, with particular emphasis on factors predisposing individuals to develop compulsive drug seeking behaviors.

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Figures

Figure 1
Figure 1. The ML-DA system

The figure shows a schematic representation of the main forebrain areas reached by the mesolimbic DA system (Swanson, 1982; German & Manaye, 1993; Haber & Fudge, 1997). According to anatomical and evolutionistic criteria (Swanson 2000), the structures innervated by ML-DA have been divided in dienchephalic, basal forebrain, and higher forebrain areas. Midbrain: VTA = ventral tegmental area Diencephalon: LH = lateral hypothalamus, LMB = lateral mammillary body Basal forebrain: Nacc = nucleus accumbens, VP = ventral pallidum, OT = olfactory tubercle, CeA = central nucleus of amygdala, MeA = medial nucleus of the amygdala, BNST = bed nucleus of stria terminalis, LS = lateral septum. Higher forebrain: pFC = prefrontal cortex, ACC = anterior cingulated cortex, BLA = basolateral amygdala, HC = hippocampal complex.

Figure 2
Figure 2. DA innervation of BG-thalamocortical circuits

All ascending mesencephalic DA projections innervate the BG rather widely, while only the ML-DA system projects to the frontal cortex. Although the DA transmission in frontal cortex has received an increasing interest, our paper is mainly focused on the role of DA release in BG. In particular, DA transmission in ventral and dorsal striatal areas (the input areas of BG) modulates the communication between glutamatergic projections arriving from frontal cortex and GABAergic neurons located inside the striatum. In such a way, DA regulates the diffusion of neural activity patterns within basal ganglia-thalamocortical circuits. The figure doesn't show the segregation of BG-thalamocortical circuits described by Alexander and coll. (1986), but the schematic representation can be applied to limbic, associative or motor loops of those circuits.

Figure 3
Figure 3. Functional feedbacks between tonic and phasic DA transmission

In the Grace model (Grace 1991; 2000), tonic DA levels were indicated to inhibit phasic DA release, since D2 autoreceptors activation decreases bursting (and firing) activity of DA neurons. Without questioning the validity of the Grace theory, our alternative model considers the existence of two different feedback loops between tonic and phasic DA transmission. The first one is well experimentally demonstrated, it acts in short-time periods, and consists of the negative influences that tonic DA exerts over DA cell bursting (as in the Grace model). However, in our alternative model, a positive feedback loop has been hypothesized (but not demonstrated yet), since its existence may help in explaining some important empirical evidence. The supposed positive feedback loop should act in longer time frames and consist in tonic DA increasing the amount (or quanta) of DA released per single burst. We called this component the relative phasic DA transmission, to distinguish it from the absolute phasic DA transmission, which is dependent upon the relative phasic DA, plus the mean bursting activity of DA neurons. In our model, tonic DA transmission increases the relative phasic DA (potentiating the efficiency of each burst), and inhibits the mean bursting activity of DA neurons, without strongly modifying the absolute phasic DA. In sum, the Grace model emphasizes the existence of a negative interaction between tonic and phasic DA, whereas our model individuates the existence of a positive feedback loop.

Figure 4
Figure 4. DA-promoted BG activity patterns

Much evidence has shown that the release of DA into BG blocks the spreading of cortical rhythms in BG structures (A). For example, DA inhibits cortically-derived beta oscillatory patterns and promotes the emergence of BG characteristic oscillatory patterns (in the gamma range) in BG-thalamocortical circuits (Brown & Mardsen, 1998; Brown, 2003; Countermanche et al., 2003; Magill et al., 2004; Lee et al., 2004; Sharrot et al., 2005). The inhibitory function of DA transmission on the spreading of cortical rhythms is mainly mediated by the activation of D2-type receptors (D2), since they have an inhibitory role over descending glutamatergic transmission into BG areas (Nicola et al., 2000; West et al., 2003; O'Donnell, 2003) (B). The consequent emergence of gamma and other BG rhythms may favors the release of neurodynamic sequences and their diffusion in BG-thalamocortical circuits. On the other hand, transient activation of D1-type receptors (D1) may have an excitatory function and seems to favor the entrance of specific and highly convergent cortical and limbic information into BG (West et al., 2003; O'Donnell, 2003) (B). Those signals may control the release of neurodynamic sequences in accordance with the representation of the organism-environment relationship. The global function of DA may then be conceptualized as a widespread modulation favoring the elaboration of relevant corticolimbic information into a BG intentional code.

Figure 5
Figure 5. The process of drugs addiction development

In the neurocognitive behavioristic perspective, addiction has been explained as the consequence of drug-induced brain adaptations “stamping” specific associative memories in neural circuits (A). The over-representation of drug-related memories should be caused by synaptic modifications connecting cortico-limbic areas (involved in the representation of motivationally relevant stimuli) to BG areas (involved in the expression of motivated and intentional behaviors). The flow of activity through which compulsive memories are expressed is a linear input-output way of processing, while the ML-DA transmission (especially into the Nacc) is supposed to be particularly important in the drug-induced reinforcement process. The affective neuroethological perspective advanced here diverges from the previous one in considering the drug-induced activation of the SEEKING emotional disposition as the cardinal element in the formation of those memories that make drugs and drug-related stimuli always more attractive (B). In particular, we think that ML-DA release after drug intake facilitates the emergence of specific neurodynamic sequences along the BG-thalamocortical circuits, which constitute the patterns through which the SEEKING disposition is expressed at the neural level. Once generated, these sequences match the representations of specific information about the environment (which are elaborated in BG-thalamocortical circuits and related structures). In line with the “Hebbian” dynamic conception of synaptic plasticity, we think that the match between SEEKING sequences and drug-related memories permanently modify the functional organization of the brain (from the molecular to the systemic level). Therefore, the cascade of neuroadaptations observed after drug use (from molecular to cellular level) represents the tendency of the SEEKING disposition to be activated by drug-related memories and expressed through drug-seeking behaviors.

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References

    1. Abercrombie ED, Keefe KA, DiFrischia DS, Zigmond MJ. Differential effect of stress on in vivo dopamine release in striatum, nucleus accumbens, and medial frontal cortex. J Neurochem. 1989;52:1655–1658. - PubMed
    1. Albin RL, Young AB, Penney JB. The functional anatomy of basal ganglia disorders. Trends Neurosci. 1989;12:366–375. - PubMed
    1. Alcaro A, Cabib S, Ventura R, Puglisi-Allegra S. Genotype- and experience-dependent susceptibility to depressive-like responses in the forced-swimming test. Psychopharmacology (Berl) 2002;164(2):138–43. - PubMed
    1. Alexander GE, DeLong MR, Strick PL. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci. 1986;9:357–381. - PubMed
    1. Alheid GF. Extended amygdala and basal forebrain. Ann N Y Acad Sci. 2003;985:185–205. - PubMed

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