The development of a conditioned place preference to morphine: Effects of microinjections into various CNS sites.

Abstract

Experiment 1 examined whether microinjections of morphine (1 microg in 0.5 microl over 1 min x 2 pairings) into 13 different CNS sites produced a conditioned place preference (CPP). Injections into the lateral ventricles (LV), ventral tegmental area (VTA), or periaqueductal gray (PAG) produced a CPP; injections 1 mm dorsal to the PAG or VTA, or into the caudate putamen, medial frontal cortex, hippocampus, lateral nucleus of the amygdala, lateral hypothalamus, pedunculopontine tegmental nucleus, posterior hypothalamus, ventral palladium, or nucleus accumbens septi (core or shell) did not. In Experiment 2, morphine 0.2 microg produced a CPP when injected into the VTA but not in the PAG, while 5.0 microg was effective in both sites. The CPP induced by systemic morphine (4 mg/kg x 1 pairing) was blocked by naloxone methiodide (NM) injected (2 nmol in 0.5 microl) into the VTA. PAG injections of 2 nmol reduced, and 5 nmol NM eliminated, the CPP. The results confirm that morphine injections into the VTA or the PAG are rewarding, that blockade of opioid receptors in either site disrupts a morphine-induced CPP, and that the VTA is more sensitive to both effects.

Identification of a Dopamine Receptor-Mediated Opiate Reward Memory Switch in the Basolateral Amygdala–Nucleus Accumbens Circuit

“…However, the significance of this DAergic VTA3 BLA projection pathway in terms of opiate reward processing is not known. Unlike the VTA, the BLA itself is not implicated in the primary rewarding effects of opiates as microinfusions of morphine directly into the amygdala fail to produce reinforcing effects (Olmstead and Franklin, 1997). BLA neuronal activity is correlated with the acquisition and recall of opiate-related associative memories (Frenois et al, 2005) and inactivation or lesions of the BLA attenuate cue-induced recall of heroin-seeking behavior (Fuchs and See, 2002), demonstrating a critical role for the BLA during opiate-related learning and memory.…”

Roles of the Nucleus Accumbens and Amygdala in the Acquisition and Expression of Ethanol-Conditioned Behavior in Mice

“…There have been mixed results as to the role of the Acb and Amy in morphine CPP. For example, there have been reports of 6-OHDA and electrolytic lesions of the Acb disrupting acquisition of morphine CPP (Kelsey et al, 1989;Shippenberg et al, 1993;White et al, 2005), whereas Olmstead and Franklin (1997) found that excitotoxic lesions of the Acb or Amy failed to disrupt acquisition of morphine CPP.…”

δ-Opioid Receptor Expression in the Ventral Tegmental Area Protects Against Elevated Alcohol Consumption

“…The ventral tegmental area (VTA) has been implicated in the motivational actions of opioids (Bozarth and Wise, 1984) and EtOH (McBride et al, 1991): injection of a -opioid receptor (MOR) agonist into the VTA is reinforcing (Bals-Kubik et al, 1993;Olmstead and Franklin, 1997;Zangen et al, 2002;Terashvili et al, 2004) while MOR antagonists in the VTA block both opioid and EtOH place preference (Phillips and LePiane, 1980;Bechtholt and Cunningham, 2005). The major reinforcing process in the VTA is thought to be excitation of dopamine (DA) neurons (Schultz, 2007) and MOR agonist-mediated reinforcement in the VTA is thought to be due to inhibition of GABA release onto DA neurons (Johnson and North, 1992).…”