Comparison of alcohol-preferring (P) and nonpreferring (NP) rats on tests of anxiety and for the anxiolytic effects of ethanol

Stewart, Robert B.; Gatto, Gregory J.; Lumeng, Lawrence; Li, T.-K.; Murphy, James M.

doi:10.1016/0741-8329(93)90046-q

Cited by 249 publications

(174 citation statements)

References 27 publications

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“…Thus, in a recent study Spanagel et al (14) showed a significantly higher intake and preference for EtOH in rats selected as anxious in the plus-maze test, which led them to suggest that the degree of anxiety may underlie, at last in part, the initial motivation to drink alcohol. These results agree with the study of Stewart et al (16) which indicated a higher degree of anxiety in EtOH-preferring than non-preferring rats.…”

Section: Discussionsupporting

confidence: 83%

“…Moreover, basic studies on labora-tory animals attempting to validate the tension-reduction hypothesis have produced conflicting results. For example, in heterogeneous populations of Wistar rats, high baseline levels of experimental anxiety have been reported to predict high voluntary EtOH self-administration (14), whereas more contradictory results have been reported with rat lines bred for EtOH preference (15,16). Since little is known about the possible interaction between experimental anxiety and the effects of alcohol, in the present study we investigated the relationship between different levels of anxiety and the reinforcing effects of EtOH in rats.…”

Section: Introductionmentioning

confidence: 98%

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Experimental anxiety and the reinforcing effects of ethanol in rats

Blatt

Takahashi

1999

Braz J Med Biol Res

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In order to examine the relationship between anxiety and reinforcing effects of alcohol, drug-naive male Wistar rats weighing 250-300 g were classified as anxious and non-anxious in the elevated plusmaze test. A conditioned place preference test was then used to investigate the reinforcing effects of ethanol (EtOH) on these animals. On 2 alternate days, groups of anxious, non-anxious and normal rats received intraperitoneal (ip) injections of EtOH (0.5, 1.0 or 1.5 g/kg) immediately before a 15-min confinement to the white compartment. On the 2 intervening days the same rats received ip injections of saline before confinement to the opposite compartment. On day 5, a 15-min free-choice test was carried out with no injections. Rats classified as anxious showed a significant, though not dosedependent preference for all doses of ethanol compared to salinetreated animals. These data demonstrate that rats regarded as anxious are more sensitive to the reinforcing effects of EtOH than nonanxious and normal Wistar rats and emphasize the relevance of the basal levels of anxiety of rats when trying to detect the reinforcing effects of EtOH.

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Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 98%

Experimental anxiety and the reinforcing effects of ethanol in rats

Blatt

Takahashi

1999

Braz J Med Biol Res

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“…Operant selfadministration is thought to more directly gauge motivation to obtain the reinforcer, whereas home cage drinking can also be controlled by taste, calories and other factors not directly related to pharmacological reinforcement. Furthermore, the P rats show elevated anxiogenic-like behavior and it has been hypothesized that their excessive ethanol drinking is in part driven by ethanol's negatively reinforcing properties (ie, reduction of anxiety symptoms) (Stewart et al, 1993). NPS has anxiolytic-like effects in animal models of anxiety (Jungling et al, 2008;Xu et al, 2004); hence it is possible that this peptide decreases the incentive for ethanol intake in P rats by partially substituting for the anxiolytic-like effects of ethanol, thus reducing the motivation to consume the drug for its negatively reinforcing properties.…”

Section: Discussionmentioning

confidence: 99%

Persistent Increase of Alcohol-Seeking Evoked by Neuropeptide S: an Effect Mediated by the Hypothalamic Hypocretin System

Cannella

Economidou

Kallupi

et al. 2009

Neuropsychopharmacol

101

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The association of ethanol's reinforcing effects with specific environmental stimuli is thought to be a critical factor for relapse risk in alcoholism. This study examined in rats the effects of a newly deorphanized neuropeptide receptor and its cognate ligand, Neuropeptide S (NPS), on ethanol consumption and reinstatement of ethanol-seeking by environmental cues previously associated with ethanol availability. In the self-administration experiments, the stable response rates observed for ethanol reinforcement were not modified by intracerebroventricular (ICV) injection of NPS (1.0 and 2.0 nmol per rat). In the reinstatement experiments, ethanol-associated cues induced robust rates of ethanol seeking, which were highly resistant to extinction over repeated sessions of reinstatement testing. ICV NPS treatment (1.0, 2.0 and 4.0 nmol per rat) resulted in a significant increase of ethanol seeking elicited by ethanol-associated cues. In contrast, NPS did not affect the reinstatement of responding to water-paired stimuli. Site-specific NPS injection (0.1 and 0.5 nmol per rat) into the lateral hypothalamus also reinstated extinguished responding to ethanol. This effect was selectively blocked by pre-treatment with the hypocretin-1/orexin-A antagonist SB-334867 (10 mg/kg, i.p.). At the dose tested, SB-334867 did not modify alcohol reinstatement per se. These results provide the first demonstration that activation of NPS receptors in the LH intensifies relapse to ethanol-seeking elicited by environmental conditioning factors. This effect is selective, and is mediated by activation of LH hypocretin neurones. Based on the present findings, we also predict that antagonism at NPS receptors could represent a novel pharmacological approach to alcohol relapse treatment.

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“…It has also been found that CREB expression and phosphorylation as well as NPY protein levels are lower in amygdaloid brain structures of alcoholpreferring (P) rats compared with alcohol-nonpreferring (NP) rats (Hwang et al, 1999;Pandey et al, 1999). Interestingly, P rats display more anxiety-like behaviors and have higher ethanol preference than NP rats Stewart et al, 1993). More recently, it was found that infusions of PKA inhibitor in the cen-tral amygdala decreased CREB phosphorylation and NPY expression and also provoked anxiety-like behaviors and increased alcohol preference in rats (Pandey et al, 2003b).…”

Section: Introductionmentioning

confidence: 96%

Partial Deletion of the cAMP Response Element-Binding Protein Gene Promotes Alcohol-Drinking Behaviors

Pandey¹,

Roy²,

Zhang³

et al. 2004

J. Neurosci.

144

128

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The cAMP response element-binding protein (CREB) gene transcription factor has been shown to play a role in the synaptic plasticity associated with drug addictive behaviors; however, the causal role of the CREB gene in alcohol-drinking behaviors is unknown. The present investigation evaluated alcohol-drinking behaviors in mice that are haplodeficient in CREB as a result of targeted CREB (␣ and ⌬) gene disruption. It was found that CREB-haplodeficient (ϩ/Ϫ) mice have higher preference for ethanol but not for sucrose solution than wild-type (ϩ/ϩ) littermates. The functional aspects of the CREB gene transcription factor were also investigated by measuring the protein levels of phosphorylated CREB (p-CREB) and the expression of cAMP-inducible genes such as neuropeptide Y (NPY) and brain-derived neurotrophic factor (BDNF). Deletion of the CREB (␣ and ⌬) gene significantly decreases total CREB, p-CREB levels and the expression of NPY and BDNF in the brain structures of CREB-deficient (ϩ/Ϫ) mice. It was also found that CREB-deficient (ϩ/Ϫ) mice displayed more anxiety-like behaviors and that acute ethanol exposure produced anxiolytic effects and significantly increased protein levels of p-CREB and NPY in the central and medial but not in the basolateral amygdala of wild-type mice, but these effects are attenuated in CREB-deficient mice compared with wild-type mice. These results provide the first direct evidence that a haplodeficiency of the CREB gene is associated with increased alcohol-drinking behaviors. Furthermore, alcohol drinking and anxiety-like behaviors in CREBhaplodeficient mice may possibly be related to decreased expression of NPY and BDNF in the brains of these mice.

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Comparison of alcohol-preferring (P) and nonpreferring (NP) rats on tests of anxiety and for the anxiolytic effects of ethanol

Cited by 249 publications

References 27 publications

Experimental anxiety and the reinforcing effects of ethanol in rats

Experimental anxiety and the reinforcing effects of ethanol in rats

Persistent Increase of Alcohol-Seeking Evoked by Neuropeptide S: an Effect Mediated by the Hypothalamic Hypocretin System

Partial Deletion of the cAMP Response Element-Binding Protein Gene Promotes Alcohol-Drinking Behaviors

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