Effects of repeated amphetamine injections on lateral hypothalamic brain stimulation reward and subsequent locomotion

Wise, Roy A.; Munn, Elizabeth

doi:10.1016/0166-4328(93)90115-7

Cited by 43 publications

(36 citation statements)

References 38 publications

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“…Previous studies evaluating the interaction between electrical stimulation and repeated drug use found lack of sensitization to the facilitating effects of cocaine on intracranial self-stimulation (Bauco and Wise, 1997), and that repeated LH self-stimulation delayed the development of behavioral sensitization to repeated administration of amphetamine (Wise and Munn, 1993). On the other hand, electrical stimulation of the VTA sensitized rats to the acute psychomotor activating effects of amphetamine (BenShahar and Ettenberg, 1994).…”

Section: Discussionmentioning

confidence: 97%

“…For example, hippocampal stimulation reinstated cocaine self-administration (Vorel et al, 2001), whereas repeated PFC stimulation sensitized cocaine-induced locomotor response (Schenk and Snow, 1994). In addition, hypothalamic intracranial self-stimulation (ICSS) delays the development of psychomotor sensitization to repeated amphetamine exposure (Wise and Munn, 1993). Finally, hypothalamic ICSS downregulates GluR1 levels in the VTA (Carlezon et al, 2001), which is opposite to the repeated cocaine exposure-induced GluR1 upregulation in the VTA (Lu et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Repeated Electrical Stimulation of Reward-Related Brain Regions Affects Cocaine But Not “Natural” Reinforcement

Levy

Shabat-Simon²,

Shalev³

et al. 2007

J. Neurosci.

126

105

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Drug addiction is associated with long-lasting neuronal adaptations including alterations in dopamine and glutamate receptors in the brain reward system. Treatment strategies for cocaine addiction and especially the prevention of craving and relapse are limited, and their effectiveness is still questionable. We hypothesized that repeated stimulation of the brain reward system can induce localized neuronal adaptations that may either potentiate or reduce addictive behaviors. The present study was designed to test how repeated interference with the brain reward system using localized electrical stimulation of the medial forebrain bundle at the lateral hypothalamus (LH) or the prefrontal cortex (PFC) affects cocaine addiction-associated behaviors and some of the neuronal adaptations induced by repeated exposure to cocaine. Repeated high-frequency stimulation in either site influenced cocaine, but not sucrose reward-related behaviors. Stimulation of the LH reduced cue-induced seeking behavior, whereas stimulation of the PFC reduced both cocaine-seeking behavior and the motivation for its consumption. The behavioral findings were accompanied by glutamate receptor subtype alterations in the nucleus accumbens and the ventral tegmental area, both key structures of the reward system. It is therefore suggested that repeated electrical stimulation of the PFC can become a novel strategy for treating addiction.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Repeated Electrical Stimulation of Reward-Related Brain Regions Affects Cocaine But Not “Natural” Reinforcement

Levy

Shabat-Simon²,

Shalev³

et al. 2007

J. Neurosci.

126

105

View full text Add to dashboard Cite

show abstract

“…This effect indicates additivity between the rewarding effects of the stimulation and the rewarding effects of the drugs, and suggests that the drugs themselves are rewarding. However, the magnitude of the acute reward-related effects of cocaine (Frank et al 1988;Bauco and Wise 1997), amphetamine (Wise and Munn 1993), morphine (Bauco and Wise 1993), PCP (Carlezon and Wise 1993), and nicotine (Bauco et al 1994) does not change progressively with repeated intermittent drug treatment in the BSR paradigm. [There is a report in which brain stimulation pre-sensitizes rats to the locomotor-stimulating effects of amphetamine (Ben-Shahar and Ettenberg 1994), but this work involved direct rather than transynaptic stimulation of the VTA, which might result in different neuroadaptations.…”

Section: Discussionmentioning

confidence: 99%

“…These findings suggest that drug reward undergoes sensitization (reverse-tolerance) with repeated intermittent treatment. However, in curve-shift variants of the BSR paradigm, similar regimens do not produce any change in the strength of the reward-related effects of these drugs: there is no evidence of sensitization (or tolerance) to the rewarding effects of cocaine (Frank et al 1988;Bauco and Wise 1997), amphetamine (Wise and Munn 1993), morphine (Bauco et al 1993), PCP (Carlezon and Wise 1993), or nicotine (Bauco and Wise 1994) with repeated intermittent treatment. These findings raise the possibility that pre-exposure to electrical stimulation of the MFB during BSR training causes adaptations that prevent further changes in the rewarding strength of the drugs.…”

mentioning

confidence: 99%

Repeated Exposure to Rewarding Brain Stimulation Downregulates GluR1 Expression in the Ventral Tegmental Area

Carlezon

Todtenkopf

McPhie

et al. 2001

Neuropsychopharmacology

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There is considerable evidence that drug reward and brain stimulation reward (BSR) share common neural substrates. Although it is known that exposure to drugs of abuse causes a variety of molecular changes in brain reward systems, little is known about the molecular consequences of BSR. We report that repeated exposure to rewarding stimulation of the medial forebrain bundle (MFB) selectively decreases expression of GluR1 (an AMPA receptor subunit) in the VTA, without effect on expression of several other proteins (GluR2, NMDAR1, tyrosine hydroxylase). This effect of BSR on GluR1 expression is opposite of that caused by intermittent exposure to cocaine and morphine, which are known to elevate GluR1 expression in the VTA. Considering that elevated GluR1 expression in the VTA has been associated with increased sensitivity to drug reward, the finding that BSR and drugs of abuse have opposite effects on GluR1 expression in this region may provide an explanation for why the reward-related effects of many drugs (cocaine, morphine, amphetamine, PCP, nicotine) Electrical brain stimulation, like intravenous administration of drugs of abuse, can establish arbitrary response habits (e.g., lever-pressing) in rats (see Wise 1996). Although there are many sites at which brain stimulation is rewarding, stimulation of the medial forebrain bundle (MFB) at the level of the lateral hypothalamus (LH) produces high response rates without evidence of aversive effects. Moreover, it is thought that the MFB is part of a final common path for the rewarding effects of brain stimulation at a variety of limbic sites (Wise 1996).Many drugs of abuse-including morphine, cocaine, amphetamine, phencyclidine (PCP), and nicotine-potentiate the rewarding impact of MFB stimulation (see Wise 1996). When tested in the "curve-shift" variant of the brain stimulation reward (BSR) paradigm, these drugs increase the potency of the stimulation, causing leftward shifts in the functions that relate response strength to stimulation strength (Gallistel and Freyd 1987;Frank et al. 1988). Such shifts suggest additivity between the rewarding effects of the drug and the rewarding effects of the stimulation. Conversely, agents that attenuate drug reward (dopamine or opioid antagonists) attenuate BSR on their own, and block the ability of drugs of abuse to cause leftward shifts (Gallistel and Freyd 1987;Rompré and Wise 1989 (Wise 1996). Together, these findings are often considered evidence that drug reward and BSR share common neural substrates. Repeated exposure to drugs of abuse can alter their rewarding effects in rats. Pre-exposure to amphetamine, cocaine, and morphine facilitates the ability of these drugs to establish conditioned place preferences (Lett 1989). Similarly, rats pre-exposed to amphetamine or cocaine learn more rapidly to self-administer these drugs intravenously (Piazza et al. 1990;Horger et al. 1990). These findings suggest that drug reward undergoes sensitization (reverse-tolerance) with repeated intermittent treatment. However, in curve-shift ...

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“…Previous experience with amphetamine (Piazza et al 1990) or cocaine (Horger et al 1990) appears to accelerate the acquisition of intravenous self-administration of these agents, and previous experience with amphetamine or morphine appears to enhance the establishment of drug-conditioned place preferences (Lett 1989). Repeated testing with amphetamine appears to enhance the reward-potentiating action of this agent in one version of the brain stimulation reward paradigm (Predy and Kokkinidis 1984) but not in the curve-shift paradigm (Wise and Munn 1993). Inasmuch as the reward-enhancing effects of drugs in the BSR paradigm are thought to reflect a summation of drug reward and brain stimulation reward (Wise et al 1992), it is thus surprising that treatments that sensitized rats to the locomotor-stimulating effects of PCP failed to sensitize them to the reward-enhancing effects of this drug.…”

Section: Discussionmentioning

confidence: 99%

Phencyclidine-induced potentiation of brain stimulation reward: acute effects are not altered by repeated administration

Carlezon

Wise

1993

Psychopharmacology

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Phencyclidine (PCP; 2.5 or 5.0 mg/kg) potentiated the effects of rewarding hypothalamic brain stimulation, causing parallel leftward shifts of the functions that relate rate of responding to stimulation frequency. Thus, like a number of other drugs of abuse, PCP lowered the "dose" of stimulation required to maintain responding at a given criterion. No progressive changes in the reward-potentiating effects of PCP were evident when the rats were tested once per week for 8 weeks; there was neither tolerance nor sensitization to the initial rewarding properties of PCP. However, in subsequent locomotor tests rats appeared to be already sensitized to PCP; this raises the possibility that the electrical stimulation of the lateral hypothalamus itself maximally sensitized the animals to the stimulant effects of the drug.

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Effects of repeated amphetamine injections on lateral hypothalamic brain stimulation reward and subsequent locomotion

Cited by 43 publications

References 38 publications

Repeated Electrical Stimulation of Reward-Related Brain Regions Affects Cocaine But Not “Natural” Reinforcement

Repeated Electrical Stimulation of Reward-Related Brain Regions Affects Cocaine But Not “Natural” Reinforcement

Repeated Exposure to Rewarding Brain Stimulation Downregulates GluR1 Expression in the Ventral Tegmental Area

Phencyclidine-induced potentiation of brain stimulation reward: acute effects are not altered by repeated administration

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