Lesions of the lateral parabrachial nucleus block the aversive motivational effects of both morphine and morphine withdrawal but spare morphine's discriminative properties

Department of Anatomy and Cell Biology, University of Toronto, Ontario, Canada.
Behavioral Neuroscience (Impact Factor: 2.73). 01/1997; 110(6):1496-502. DOI: 10.1037/0735-7044.110.6.1496
Source: PubMed


This study examined if the aversive properties of morphine, the aversive properties of morphine withdrawal, and the discriminative properties of morphine are mediated by common neurobiological substrates. Lesions of the lateral parabrachial nucleus, which blocked the aversive properties of morphine in the conditioned taste aversion paradigm, also blocked the acquisition of conditioned place aversions to environments paired with the aversive properties of morphine withdrawal in morphine-dependent rats. When morphine and saline were used as cues in a discrimination task, however, both sham-operated and lesioned rats were able to solve the task.

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    • "Specifically, aversive anatomical systems that include the LPBe nucleus may be activated naturally via taste (Yamamoto et al. 1994a), visceral aversive (Mediavilla et al. 2000, 2005), or nociceptive (Bernard et al. 1994) stimuli, and could be blocked by tiapride, a D2/D3 antagonist. Furthermore, it is possible that aversive brain systems that include the LPBe nucleus and dopamine neurotransmission can also be activated by artificial agents, such as drugs of abuse (Bechara et al. 1993, Nader et al. 1996) or by the intracranial electrical stimulation applied in the present study. "
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    ABSTRACT: The parabrachial complex has been related to various rewarding or aversive behavioral processes, including taste aversion learning and conditioned place aversion. This study examined the effect of tiapride, an antagonist of D2/D3 dopaminergic receptors, on place aversion induced by electrical stimulation of the external lateral parabrachial (LPBe) nucleus. Results obtained show that brain-stimulated animals avoid the area of the maze associated with electrical stimulation but show no such behavioral rejection when they receive an injection of 30 mg/kg tiapride. Furthermore, tiapride did not appear to affect the horizontal motor activity (crossing) of the animals. These results are discussed in the context of the different natural and artificial modalities used to induce aversive behavior and their relationship with dopamine systems.
    Acta neurobiologiae experimentalis 09/2014; 74(3):307-16. · 1.29 Impact Factor
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    • "The Lateral Parabrachial (LPB) complex appears to participate in neurobiological systems related to the motivational or hedonic evaluation of rewarding natural products and other substances for which preference has been acquired by learning (Calingasan & Ritter, 1993; Edwards & Ritter, 1989; Yamamoto & Sawa, 2000a, 2000b; Yamamoto et al., 2009). Thus, it has been related to the aversive processing of lithium chloride (Sakai & Yamamoto, 1997; Yamamoto & Sawa, 2000a) and drugs of abuse, such as opiates (Bechara, Martin, Pridgar, & Van der Kooy, 1993; Nader, Bechara, & Van der Kooy, 1996), and in the processing of pain and its affective components (Bernard, Huang, & Besson, 1994; Bester , Menendez, Besson, & Bernard, 1995; Jasmin, Burkey, Card, & Basbaum, 1997). The external Lateral Parabrachial (LPBe) nucleus is located in the ventral region of the lateral parabrachial complex (Fulwiler & Saper, 1984; Herbert & Bellintani-Guardia, 1995) and has been related to various homeostatic, sensory, and learning processes (De Lacalle & Saper, 2000; Edward & Ritter, 1989; Karimnamazi, Travers, & Travers, 2002; Mediavilla, Molina, & Puerto, 2000; Yamamoto, Shimura, Sakai, & Ozaki, 1994). "
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    ABSTRACT: The lateral parabrachial complex has been related to various emotional-affective processes. It has been shown that electrical stimulation of the external lateral parabrachial (LPBe) nucleus can induce reinforcing effects in place preference and taste discrimination tasks but does not appear to support self-stimulation. This study examined the relative relevance of place and taste stimuli after electrical stimulation of the LPBe nucleus. A learning discrimination task was conducted that simultaneously included both sensory indexes (taste and place) in order to determine the preference of animals for one or the other. After a taste stimulus reversal task, the rewarding effect of stimulation was found to be preferentially associated with place. These results are discussed in the context of the rewarding action and biological constraints induced by different natural and artificial reinforcing agents.
    Neurobiology of Learning and Memory 12/2013; 107. DOI:10.1016/j.nlm.2013.11.010 · 3.65 Impact Factor
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    • "Thus, it was predicted that intra-VTA and intra-PAG morphine would substitute for systemic morphine in the present study, and intra-VTA and intra- PAG NLX would reduce morphine-appropriate responding engendered by systemic morphine administration. The role of the PBN in morphine discrimination has been examined previously only in studies using a CTA procedure (Jaeger and van der Kooy, 1993, 1996; Nader et al., 1996). Although PBN is known to be critical in establishing CTA (Spector et al., 1992; Aguero et al., 1993), it is not known whether it is involved in morphine discrimination per se (using any training procedure). "
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    ABSTRACT: Previous studies have produced mixed results about the role of the ventral tegmental area, periaqueductal gray and parabrachial nucleus in morphine discriminations, perhaps owing to the considerably different methodologies used. The purpose of the present study was to compare the roles of these three brain areas using the same food-reinforced discrimination protocol, to determine whether the schedule of reinforcement influenced maximal substitution produced by site-specific morphine administration and to determine whether the time course of substitution differed by site of morphine administration. Rats were trained to discriminate 3.0 mg/kg subcutaneous morphine from saline under variable interval 15-s or fixed ratio 10 schedules of food reinforcement. Rats were then implanted with one cannula aimed at the lateral ventricle (intracerebroventricular) and one aimed at the ventral tegmental area, periaqueductal gray or parabrachial nucleus. Morphine discrimination curves were obtained by subcutaneous, intracerebroventricular and intrasite routes. When administered subcutaneously, morphine was equipotent in variable interval-trained and fixed ratio-trained rats, although it was more potent in fixed ratio-trained females than fixed ratio-trained males. When administered intracerebroventricularly, morphine (0.3-10 microg) engendered a maximum average of 63% drug-appropriate responding in both variable interval-trained and fixed ratio-trained rats; females showed significantly greater drug-appropriate responding than males, again under the fixed ratio but not under the variable interval schedule. In variable interval-trained rats, intrasite infusions of morphine (0.3-10 microg) produced maximal drug-appropriate responding of approximately 57% (ventral tegmental area), 56% (periaqueductal gray) and 41% (parabrachial nucleus); mean maximal substitution was slightly (< or = 17%) greater in fixed ratio-trained rats. When injected into the ventral tegmental area or periaqueductal gray, but not the parabrachial nucleus, naloxone methiodide (2 microg) significantly decreased drug-appropriate responding following 3.0 mg/kg subcutaneous morphine, in both variable interval-trained and fixed ratio-trained rats. The time course of the discriminative stimulus effects of morphine differed among the three brain sites: intraventral tegmental area morphine produced peak drug-appropriate responding by 15 min after injection, whereas the discriminative stimulus effects of intraperiaqueductal gray and intraparabrachial nucleus morphine peaked at approximately 60 min after injection. Taken together, these results indicate that ventral tegmental area, periaqueductal gray and parabrachial nucleus each play a role in the ability of morphine to function as a discriminative stimulus, regardless of the sex of the subject or the schedule under which the subjects are responding. Ventral tegmental area and periaqueductal gray, however, appear to be more critical than parabrachial nucleus in mediating the discriminative effects of systemic morphine in rats responding under a food reinforcement procedure. The pretreatment time and, to a lesser extent, the schedule of reinforcement are additional variables that should be considered when comparing the relative roles of different brain areas in drug discrimination.
    Behavioural Pharmacology 06/2006; 17(3):259-70. DOI:10.1097/00008877-200605000-00007 · 2.15 Impact Factor
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