Endogenous opioids mediate basal hedonic tone independent of dopamine d-1 or d-2 receptor activation

Food-associated cues alter forebrain functional connectivity as assessed with immediate early gene and proenkephalin expression

“…Enkephalin and its μ-receptor have been widely implicated in the hedonic aspects of food and drug intake [104-108]. Stimulation of μ-opioid receptors in the ventral striatum increases the intake of palatable food [36-38,109].…”

Prenatal exposure to valproic acid disturbs the enkephalinergic system functioning, basal hedonic tone, and emotional responses in an animal model of autism

“…Previous studies have implicated the nucleus accumbens and the amygdala as potential sites of action for naloxone-induced aversion and have suggested reduction in dopaminergic activity as a mediator of the effect of naloxone (Shippenberg and Bals-Kubik 1995;Stinus et al 1990). Noteworthy, recent studies indicate that naloxone may act downstream of dopamine systems to produce aversion and implicate the ventral pallidum as a potential site of its action (Narayanan et al 2004). The ventral pallidum receives a dense enkephalinergic input from the nucleus accumbens (Napier et al 1983) and local microinjections of naloxone into this structure results in CPA, probably by counteracting the endogenous enkephalinergic tone in the ventral striatopallidal pathways (Skoubis and Maidment 2003).…”

“…Endogenous opioid peptides have been also postulated to be key regulators of the basal hedonic state of the organism (Koob and Le Moal 2001;Narayanan et al 2004). Blockade of opioid receptors with the general opioid antagonists naloxone and naltrexone is dysphoric in humans (Grevert and Goldstein 1977;Hollister et al 1981;Martin del Campo et al 1992) and produces robust conditioned aversive responses in animals (Mucha et al 1985;Parker and Rennie 1992;Skoubis et al 2001).…”

“…Biochemical studies have been accompanied by examination of the VPA rats' ability to demonstrate a conditioned place aversion (CPA) to naloxone, a procedure used for assessing basal hedonic tone in rodents (Narayanan et al 2004;Skoubis et al 2005). In addition, anxiety and susceptibility to phobic states were measured in the elevated plus maze test according to the theoretical frame proposed by File et al (1993).…”

Lack of genotype effect on D1, D2 receptors and dopamine transporter binding in triple MOP‐, DOP‐, and KOP‐opioid receptor knockout mice of three different genetic backgrounds

“…Moreover, acute administration of a nonselective opioid receptor antagonist nalmefene produced an increase in D1 binding ([ 11 C]SCH23390) potential in the striatum of rats as measured by positron emission tomography (PET) (Unterwald et al, 1997) suggesting that pharmacological blockade of opioid receptors could modulate DA D1 receptors. However, another study showed that naloxone-induced conditioned place aversion is maintained in D1 receptor KO mice suggesting that endogenous opiate-mediated hedonic homeostasis is not dependent on the presence of D1 receptors (Narayanan et al, 2004). Although blockade of opioid receptors by using nonselective antagonists can modulate D1 receptors, the long-term ablation of all three opioid receptors afforded by the triple KO mice strongly suggest that a tonic role of opioid systems in the modulation of D1 receptors is lacking and provide compelling evidence that modulation of D1 receptors is not dependent on the presence of all three opioid receptors.…”