A test of the opponent‐process theory of motivation using lesions that selectively block morphine reward

Abstract

The opponent-process theory of motivation postulates that motivational stimuli activate a rewarding process that is followed by an opposed aversive process in a homeostatic control mechanism. Thus, an acute injection of morphine in nondependent animals should evoke an acute rewarding response, followed by a later aversive response. Indeed, the tegmental pedunculopontine nucleus (TPP) mediates the rewarding effects of opiates in previously morphine-naive animals, but not other unconditioned effects of opiates, or learning ability. The aversive opponent process for acute morphine reward was revealed using a place-conditioning paradigm. The conditioned place aversion induced by 16-h spontaneous morphine withdrawal from an acute morphine injection in nondependent rats was abolished by TPP lesions performed prior to drug experience. However, TPP-lesioned rats did show conditioned aversions for an environment paired with the acute administration of the opioid antagonist naloxone, which blocks endogenous opioids. The results show that blocking the rewarding effects of morphine with TPP lesions also blocked the opponent aversive effects of acute morphine withdrawal in nondependent animals. Thus, this spontaneous withdrawal aversion (the opponent process) is induced by the acute rewarding effects of morphine and not by other unconditioned effects of morphine, the pharmacological effects of morphine or endogenous opioids being displaced from opiate receptors.

An Anatomical Basis for Opponent Process Mechanisms of Opiate Withdrawal

“…Further research will be necessary to directly determine whether this dopaminergic link between the VTA and the extended amygdala is in fact involved in anxiety following acute opiate exposure. In addition to the extended amygdala, the tegmental pedunculopontine nucleus (PPTg) is important in the development of an opponent process following opiate exposure (Vargas-Perez et al, 2007; 2009). The PPTg sends excitatory glutamatergic and cholinergic inputs to dopamine cells (Oakman et al, 1995; Geisler et al, 2007) and its role in opiate reward and withdrawal may therefore be mediated by its ability to drive VTA dopaminergic activity (Pan and Hyland, 2005).…”

Opioid-induced rewards, locomotion, and dopamine activation: A proposed model for control by mesopontine and rostromedial tegmental neurons

“…PPTg or LDTg excitotoxic lesions also block morphine-induced locomotion or stereotypy (Bechara and van der Kooy, 1992; Forster et al, 2002a; Miller et al, 2002; Olmstead and Franklin, 1994a). PPTg excitotoxic lesions block the acquisition of morphine or heroin CPP and the acquisition of heroin self-administration in drug-naïve rats (Bechara et al, 1992; Nader and van der Kooy, 1997; Nader et al, 1994; Olmstead and Franklin, 1993; 1994b; Olmstead et al, 1998; Vargas-Perez et al, 2007). …”

“…Accordingly, the PPTg has been suggested to be part of a DA-independent mechanism, likely involving its descending projections (Heinmiller et al, 2009), important for opioid reward in drug-naïve animals (Bechara et al, 1998; Nader et al, 1997; Ting-A-Kee and van der Kooy, 2012). Dorsal tegmental outputs become less important for opioid CPP and self-administration after opioid dependence and withdrawal while DA output becomes more important (Bechara and van der Kooy, 1989; Bechara et al, 1998; 1992; Laviolette and van der Kooy, 2001; Laviolette et al, 2004; Nader and van der Kooy; 1997; Nader et al, 1997; 1994; Vargas-Perez et al, 2009; 2007; Ting-A-Kee and van der Kooy, 2012). Importantly, the effects of LDTg lesions on opioid reward in drug-experienced animals have not been tested.…”

Glutamate Mechanisms Underlying Opiate Memories

“…1n). As in the accumbens, this might occur by reducing excessive glutamate release from afferent inputs, and the pedunculopontine tegmental (PPT) area is one likely candidate (Vargas-Perez et al 2007; Ting-A-Kee and van der Kooy 2012).…”