Increased sensitivity to the locomotor depressant effect of a dopamine receptor antagonist during cocaine withdrawal in the rat

Baldo, Brian A.; Markou, Athina; Koob, George F.

doi:10.1007/s002130050817

Cited by 14 publications

(9 citation statements)

References 48 publications

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“…1, after 46 h of deprivation from a sweet-fat chow, rats that previously had 2 h access showed fewer instances of cage-crossing compared with ad libitum fed controls (standard rodent chow or high-fat, sweet rodent chow). Hypoactivity has been noted during cocaine withdrawal in rodents [41]. However, no signs of opiate-like withdrawal were noted in the other tests performed on this group, such as the somatic measures of withdrawal.…”

Section: Discussionmentioning

confidence: 75%

Rats that binge eat fat-rich food do not show somatic signs or anxiety associated with opiate-like withdrawal: Implications for nutrient-specific food addiction behaviors

Bocarsly¹,

Berner²,

Hoebel³

et al. 2011

Physiology & Behavior

109

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Previous studies suggest that binge eating sugar leads to behavioral and neurochemical changes similar to those seen with drug addiction, including signs of opiate-like withdrawal. Studies are emerging that show multiple neurochemical and behavioral indices of addiction when animals overeat a fat-rich diet. The goal of the present study was to utilize liquid and solid diets high in sugar and fat content to determine whether opiate-like withdrawal is seen after binge consumption of these diets in Sprague Dawley rats. Control groups were given ad libitum access to the sweet-fat food or standard chow. All rats were then given a battery of tests to measure signs of opiate-like withdrawal, which included somatic signs of distress, elevated plus-maze anxiety, and locomotor hypoactivity. Neither naloxone-precipitated (3 mg/kg) nor deprivation-induced withdrawal was observed in rats that were maintained on a nutritionally complete pelleted sweet-fat diet, a sweet, high-fat diet supplemented with standard rodent chow, or a liquid sweet-fat food. Further, body weight reduction to 85%, which is known to potentiate the reinforcing effects of substance of abuse, did not affect naloxone-precipitated signs of opiate-like withdrawal. Thus, unlike previous findings reported regarding rats with binge access to a sucrose solution, rats that binge eat sweet-fat combinations do not show signs of opiate-like withdrawal under the conditions tested. These data support the idea that excessive consumption of different nutrients can induce behaviors associated with addiction in different ways, and that the behaviors that could characterize “food addiction” may be subtyped based on the nutritional composition of the food consumed.

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Section: Discussionmentioning

confidence: 75%

Rats that binge eat fat-rich food do not show somatic signs or anxiety associated with opiate-like withdrawal: Implications for nutrient-specific food addiction behaviors

Bocarsly¹,

Berner²,

Hoebel³

et al. 2011

Physiology & Behavior

109

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“…Decreased dopaminergic function achieved through post-synaptic receptor blockade has long been associated not only with deficits in cocaine reward but also with deficits in motoric capacity (Ahlenius et al, 1987; Baldo et al, 1999; Chan and Webster, 1971; Delfs et al, 1990). Indeed, several investigators have suggested that a drug’s capacity to enhance locomotor activity serves as a predictor of, or is associated with, the reinforcing actions of the drug (e.g.…”

Section: Discussionmentioning

confidence: 99%

The dopamine antagonist cis-flupenthixol blocks the expression of the conditioned positive but not the negative effects of cocaine in rats

Wenzel

Shelton

et al. 2013

Pharmacology Biochemistry and Behavior

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Human cocaine users report that the initial “high” produced by cocaine administration is followed by an anxiogenic “crash”. Given that cocaine has such robust and opposing properties, it is likely that both the positive and negative effects of cocaine contribute to an individual’s motivation to administer the drug. Despite this likelihood, the neurobiology underlying cocaine’s dual processes remains unclear. While much literature supports a role for dopamine (DA) in cocaine reward, it is uncertain if DA also contributes to the drug’s negative effects. Our laboratory has extensively utilized a modified conditioned place test to explore cocaine’s opponent processes. In this paradigm rats develop conditioned place preferences (CPPs) for an environment paired with the immediate/positive effects of cocaine, and conditioned place aversions (CPAs) for an environment paired with the delayed/negative effects present 15-min after i.v. injection. In the current study rats were conditioned to associate an environment with either the immediate or delayed effects of i.v. cocaine (1 mg/kg/0.1 ml) three hours after i.p. pre-treatment with either the DA D1/D2 receptor antagonist cis-flupenthixol (0.5 mg/kg/ml) or saline vehicle. As expected, vehicle-treated control animals developed the normal pattern of CPPs for cocaine’s immediate effects or CPAs for the delayed effects of cocaine. However, while DA receptor antagonism prevented the expression of cocaine CPPs it did not alter the expression of cocaine-induced CPAs. These data confirm a role for DA transmission in cocaine reward but suggest that different neural pathways mediate the drug’s negative/anxiogenic properties.

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“…In rats, withdrawal from cocaine is associated with increased anxiety-like behavior in the elevated plus maze [22, 23]. Cocaine withdrawal, however, also suppresses locomotor activity [24, 25], which may yield a false-positive result in the light-dark box test. Therefore, locomotor activity was also assessed during the time spent in the dark compartment in the present study.…”

Section: Introductionmentioning

confidence: 99%

Withdrawal from chronic cocaine administration induces deficits in brain reward function in C57BL/6J mice

Stoker

Markou

2011

Behavioural Brain Research

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Anhedonia is a major symptom of cocaine withdrawal, whereas euphoria characterizes the effects of acute administration of this drug in humans. These mood states can be measured quantitatively in animals with brain reward thresholds obtained from the intracranial self-stimulation (ICSS) procedure. Studies have previously reported the reward-enhancing effects of acute cocaine administration using the ICSS procedure in mice, but the effects of chronic cocaine administration and withdrawal on brain reward thresholds have not been widely investigated in this species. Cocaine withdrawal was induced in C57BL/6J mice by removal of intraperitoneal osmotic minipumps that delivered cocaine (90 or 180 mg/kg/day, salt) for 72 h. Mice were tested in the ICSS procedure 3–100 h post-pump removal. Anxiety-like behavior was assessed in the light-dark box 24 h post-pump removal. After an 18-day washout period, tolerance and sensitization to the reward-enhancing effects of cocaine were assessed by injecting bolus cocaine intraperitoneally (0, 2.5, 5, and 10 mg/kg). The results indicated that 72 h administration of 90 and 180 mg/kg/day cocaine significantly lowered brain reward thresholds. Withdrawal from 90 and 180 mg/kg/day of cocaine administration elevated ICSS thresholds to similar extents. No anxiety-like behavior was observed in the light-dark box during withdrawal from chronic cocaine administration, although the number of transitions between compartments and locomotion in the dark compartment markedly decreased. Chronic cocaine administration did not induce tolerance or sensitization to the reward-enhancing effects of acute cocaine. In conclusion, alterations in mood states induced by cocaine administration and withdrawal in mice can be measured using the ICSS procedure.

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Increased sensitivity to the locomotor depressant effect of a dopamine receptor antagonist during cocaine withdrawal in the rat

Cited by 14 publications

References 48 publications

Rats that binge eat fat-rich food do not show somatic signs or anxiety associated with opiate-like withdrawal: Implications for nutrient-specific food addiction behaviors

Rats that binge eat fat-rich food do not show somatic signs or anxiety associated with opiate-like withdrawal: Implications for nutrient-specific food addiction behaviors

The dopamine antagonist cis-flupenthixol blocks the expression of the conditioned positive but not the negative effects of cocaine in rats

Withdrawal from chronic cocaine administration induces deficits in brain reward function in C57BL/6J mice

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