Evidence for the role of dopamine D1 receptors in morphine induced stereotypic behavior

Pollock, Jondavid; Kornetsky, Conan

doi:10.1016/0304-3940(89)90094-3

Cited by 35 publications

(10 citation statements)

References 12 publications

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“…This approach has the additional advantage of controlling for gnawingFa frequent behavior specifically engendered by LgA to heroin self-administrationFthat may have confounded the present study (Pollock and Kornetsky, 1989;. For instance, it is possible that LgA rats showed reduced heroin demand in the presence of food, not because of the increased value of food (as presumed here), but because food pellets would allow LgA rats to gnaw and to relieve an 'akathisia-like' effect induced by escalated heroin intake.…”

Section: Discussionmentioning

confidence: 93%

Supply of a Nondrug Substitute Reduces Escalated Heroin Consumption

Lenoir

Ahmed

2007

Neuropsychopharmacol

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Escalation of drug consumptionFa hallmark of addictionFhas been hypothesized to be associated with a relative devaluation of alternative nondrug rewards and thus with a decrease in their ability to compete with or to substitute for the drug. In a behavioral economic framework, decreased substitutability of nondrug rewards for drug would explain why drug consumption is behaviorally dominant and relatively resistant to change (eg price-inelastic) in drug-addicted individuals. The goal of the present study was to test this hypothesis using a validated rat model of heroin intake escalation. Escalation was precipitated by long (6 h, long access (LgA)), but not short (1 h, short access (ShA)), daily access to i.v. heroin self-administration. After escalation, the effects of price (ie fixed-ratio value) on heroin consumption were assessed under two alternative reward conditions: in the presence or absence of a nondrug substitute for heroin (ie four freely available chow pellets). As expected, escalated heroin consumption by LgA rats was less sensitive to price than heroin consumption by ShA rats, showing that heroin had acquired greater reinforcing strength during escalation. However, supplying a substitute during access to heroin was sufficient to reverse this post-escalation increase in the reinforcing effectiveness of heroin. Thus, escalated heroin consumption is not associated with a decreased sensitivity to competing nondrug rewards. Escalated drug use may therefore persist, not so much because of a relative devaluation of nondrug substitutes, but because of a loss or reduction of their availability.

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Section: Discussionmentioning

confidence: 93%

Supply of a Nondrug Substitute Reduces Escalated Heroin Consumption

Lenoir

Ahmed

2007

Neuropsychopharmacol

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“…This rightward shift is unlikely the consequence of increased heroin-induced sedation or motor stereotypy as LgA rats responded more than ShA rats on the heroinassociated lever during reinstatement testing (see below). Moreover, although half of LgA rats developed self-injury during long-access sessions of heroin self-administrationF a direct consequence of opiate-induced oral stereotypy (Pollock and Kornetsky, 1989)Fthis maladaptive behavior was not seen during reinstatement testing. In fact, LgA rats with self-injurious behavior did not differ from other LgA rats during reinstatement testing (not shown).…”

Section: Discussionmentioning

confidence: 95%

Heroin-Induced Reinstatement is Specific to Compulsive Heroin Use and Dissociable from Heroin Reward and Sensitization

Lenoir¹,

Ahmed²

2006

Neuropsychopharmacol

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Increased drug availability can precipitate a rapid transition to compulsive drug use in both vulnerable humans and laboratory animals. Recent studies have shown that despite equivalent levels of psychomotor sensitization, only rats with prolonged, but not limited, access to cocaine self-administration respond to the priming effects of cocaine on drug seeking, as measured in a within-session reinstatement model of drug craving. In this model, drug seeking is first extinguished and then reinstated by non-contingent presentations of the drug alone in the absence of response-contingent stimuli. Here, we assessed the generality of this observation in rats with daily short (1 h, ShA) vs long access (6 h, LgA) to i.v. heroin self-administration. As expected, heroin intake by LgA rats (n ¼ 24) increased over time to become excessive compared to heroin intake by ShA rats (n ¼ 24). After escalation, LgA rats tended to be less sensitive to heroin-induced locomotion (7.5-30 mg, i.v.) than ShA rats. In contrast, only LgA rats, not ShA rats, responded to the priming effects of heroin, as measured by the ability of heroin alone (7.5-30 mg, i.v.) to reinstate extinguished drug-seeking behavior. Finally, during the course of heroin intake escalation, a large proportion of LgA rats developed self-injury (mostly targeting the nails and digit tips of the forepaws), a negative consequence not seen in ShA rats. This study reproduces and extends previous research on compulsive cocaine use by showing that heroin-induced reinstatement is also specific to compulsive drug use and dissociable from heroin-induced reward and psychomotor sensitization. Neuropsychopharmacology (2007) 32, 616-624.

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“…Repeated morphine administration was shown to induce motor stereotypies (Pollock and Kornetsky, 1989; Walter and Kuschinsky, 1989) and opiate abstinence to produce excessive grooming and deficient spatial alternation, suggestive of stereotypes/perseverative behavior (Goeldner et al, 2011; Lutz et al, 2014). Concerning alcohol, early withdrawal causes stereotypic behavior in mice (Becker et al, 1987).…”

Section: Discussionmentioning

confidence: 99%

Differential behavioral and molecular alterations upon protracted abstinence from cocaine versus morphine, nicotine, THC and alcohol

2016

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Unified theories of addiction are challenged by differing drug-seeking behaviors and neurobiological adaptations across drug classes, particularly for narcotics and psychostimulants. We previously showed that protracted abstinence to opiates leads to despair behavior and social withdrawal in mice, and we identified a transcriptional signature in the extended amygdala that was also present in animals abstinent from nicotine, i9-tetrahydrocannabinol (THC) and alcohol. Here we examined whether protracted abstinence to these 4 drugs would also share common behavioral features, and eventually differ from abstinence to the prototypic psychostimulant cocaine. We found similar reduced social recognition, increased motor stereotypies, and increased anxiety with relevant c-fos response alterations in morphine, nicotine, THC and alcohol abstinent mice. Protracted abstinence to cocaine, however, led to strikingly distinct, mostly opposing adaptations at all levels, including behavioral responses, neuronal activation and gene expression. Together, these data further document the existence of common hallmarks for protracted abstinence to opiates, nicotine, THC and alcohol that develop within motivation/emotion brain circuits. In our model however, these do not apply to cocaine, supporting the notion of unique mechanisms in psychostimulant abuse.

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Evidence for the role of dopamine D1 receptors in morphine induced stereotypic behavior

Cited by 35 publications

References 12 publications

Supply of a Nondrug Substitute Reduces Escalated Heroin Consumption

Supply of a Nondrug Substitute Reduces Escalated Heroin Consumption

Heroin-Induced Reinstatement is Specific to Compulsive Heroin Use and Dissociable from Heroin Reward and Sensitization

Differential behavioral and molecular alterations upon protracted abstinence from cocaine versus morphine, nicotine, THC and alcohol

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