Localizations and Projections of Brain Stress Systems?Vasopressin

Vasopressin mRNA levels were increased selectively in the amygdala during early spontaneous withdrawal from heroin, and a selective V_1b receptor antagonist, SSR149415, blocked footshock-induced reinstatement of heroin-seeking behavior, suggesting that vasopressin systems in the amygdala may be a key component of the aversive emotional consequences of opioid withdrawal (Zhou et al., 2008). Prolonged or chronic ethanol exposure decreased vasopressin-like immunoreactivity in the hypothalamus and the bed nucleus of the stria terminalis projection to the lateral septum (Gulya et al., 1991). A selective V_1b receptor antagonist dose-dependently blocked the increase in ethanol self-administration during withdrawal in dependent rats but had no effect in nondependent animals (S. Edwards et al., 2008, Soc. Neurosci., abstract). To date, few studies have explored the motivational effects of vasopressin antagonists in animal models of dependence or stress-induced reinstatement with other drugs of abuse. However, the literature suggesting that V_1b antagonists have anxiolytic-like profiles (see Supplemental Data) and that vasopressin and its receptors are highly expressed in the extended amygdala lends credence to the hypothesis that vasopressin systems in the extended amygdala may have a role in the increased alcohol intake associated with dependence.

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Brain Antistress Systems and Addiction: Neuropeptide Y and Nociceptin

Neuropeptide Y

Neuropeptide Y (NPY) is a 36 amino acid polypeptide with powerful orexigenic and anxiolytic-like actions (see Supplemental Data). NPY is distributed widely throughout the central nervous system but with high concentrations in the extended amygdala (Adrian et al., 1983) (Figure 8). Multiple NPY receptor subtypes have been identified, with the Y₁ and Y₂ subtypes most implicated in stress and drug actions. The Y₁ receptor has a wide distribution throughout the rat brain, where it is most abundantly found in the cortex, olfactory tubercle, hippocampus, hypothalamus, and thalamus (Parker and Herzog, 1999). The distribution of Y₂ receptors is similar to that of Y₁ receptors, although Y₂ receptor expression is less abundant in the cortex and thalamus and more abundant in the hippocampus (Parker and Herzog, 1999). Y₁ receptors are hypothesized to be postsynaptic and Y₂ receptors presynaptic (Heilig and Thorsell, 2002).

Figure 8

Date: 2016-06-12; view: 334