Oral drug self-administration in the home cage of mice: alcohol-heightened aggression and inhibition by the 5-HT 1B agonist anpirtoline

Miczek, Klaus A.; Almeida, Rosa M. M. de

doi:10.1007/s002130100831

Cited by 84 publications

(80 citation statements)

References 42 publications

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“…Every fifth response (fixed ratio 5) was reinforced by the delivery of an Alc solution and the secondary cues of an audible click and absence of the house light. A modified sucrose-fading procedure facilitated Alc self-administration (described in Miczek and de Almeida, 2001). Drinking sessions occurred 5 days per week between 0800 and 1400 h.…”

Section: Alcohol Self-administrationmentioning

confidence: 99%

Escalated Aggression after Alcohol Drinking in Male Mice: Dorsal Raphé and Prefrontal Cortex Serotonin and 5-HT1B Receptors

Faccidomo

Bannai

Miczek

2008

Neuropsychopharmacol

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A significant minority of individuals engages in escalated levels of aggression after consuming moderate doses of alcohol (Alc). Neural modulation of escalated aggression involves altered levels of serotonin (5-HT) and the activity of 5-HT 1B receptors. The aim of these studies was to determine whether 5-HT 1B receptors in the dorsal raphé (DRN), orbitofrontal (OFC), and medial prefrontal (mPFC) cortex attenuate heightened aggression and regulate extracellular levels of 5-HT. Male mice were trained to self-administer Alc by performing an operant response that was reinforced with a delivery of 6% Alc. To identify Alc-heightened aggressors, each mouse was repeatedly tested for aggression after consuming either 1.0 g/kg Alc or H 2 O. Next, a cannula was implanted into either the DRN, OFC, or mPFC, and subsets of mice were tested for aggression after drinking either Alc or H 2 O prior to a microinjection of the 5-HT 1B agonist, CP-94,253. Additional mice were implanted with a microdialysis probe into the mPFC, through which CP-94,253 was perfused and samples were collected for 5-HT measurement. Approximately 60% of the mice were more aggressive after drinking Alc, confirming the aggression-heightening effects of 1.0 g/kg Alc. Infusion of 1 mg CP-94,253 into the DRN reduced both aggressive and motor behaviors. However, infusion of 1 mg CP-94,253 into the mPFC, but not the OFC, after Alc drinking, increased aggressive behavior. In the mPFC, reverse microdialysis of CP-94,253 increased extracellular levels of 5-HT; levels decreased immediately after the perfusion. This 5-HT increase was attenuated in self-administering mice. These results suggest that 5-HT 1B receptors in the mPFC may serve to selectively disinhibit aggressive behavior in mice with a history of Alc self-administration.

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Section: Alcohol Self-administrationmentioning

confidence: 99%

Escalated Aggression after Alcohol Drinking in Male Mice: Dorsal Raphé and Prefrontal Cortex Serotonin and 5-HT1B Receptors

Faccidomo

Bannai

Miczek

2008

Neuropsychopharmacol

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“…Evidence for alcohol as a promoter of escalated levels of aggressive behavior has been established in laboratory settings, particularly in susceptible subgroups of individuals (Cloninger, 1987;Miczek et al, 2004). In mice, low to moderate doses of alcohol can escalate aggressive behaviors to levels that are significantly higher and more injurious than species-typical aggression (Miczek et al, 1998;Miczek and de Almeida, 2001), modeling critical features of alcoholescalated aggression.…”

Section: Introductionmentioning

confidence: 99%

Prevention of Alcohol-Heightened Aggression by CRF-R1 Antagonists in Mice: Critical Role for DRN-PFC Serotonin Pathway

Quadros

Hwa

Shimamoto

et al. 2014

Neuropsychopharmacol

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Alcohol can escalate aggressive behavior in a significant subgroup of rodents, humans, and nonhuman primates. The present study investigated whether blockade of corticotropin-releasing factor receptor type 1 (CRF-R1) could prevent the emergence of alcoholheightened aggression in mice. The serotonin (5-HT) pathway from the dorsal raphe nucleus (DRN) to the medial prefrontal cortex (mPFC) by CRF-R1 was investigated as a possible target for the prevention of alcohol-heightened aggressive behavior. Male CFW mice that reliably exhibited aggressive behaviors after consuming 1 g/kg of alcohol received systemic or intra-DRN administration of CRF-R1 antagonists, CP-154,526 or MTIP, before a confrontation with a male conspecific. Blockade of DRN CRF-R1 receptors with both antagonists significantly reduced only alcohol-heightened aggression, whereas systemic administration reduced both alcohol-heightened and species-typical aggression. Next, a 5-HT1A agonist, 8-OH-DPAT, was coadministered with CP-154,526 into the DRN to temporarily disrupt 5-HT activity. This manipulation abolished the antiaggressive effects of intra-DRN CP-154,526. In the mPFC, in vivo microdialysis revealed that extracellular 5-HT levels were increased in mice that consumed alcohol and were then injected with CP-154,526, both systemically or intra-DRN. Neither alcohol nor CP-154,526 alone affected 5-HT release in the mPFC. The present results suggest the DRN as a critical site for CRF-R1 to modulate alcohol-heightened aggression via action on the serotonergic DRN-PFC pathway.

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“…Experimental deletion of the gene coding for the 5-HT 1B receptor as well as pharmacological studies implicate this receptor subtype in aggressive behavior (Saudou et al 1994;Mos et al 1992). Agonists at postsynaptic 5-HT 1B receptors, such as CP-94,253, zolmitriptan, and anpirtoline, produce remarkably specific inhibition of species-typical aggression and very intense and frequent aggressive behavior at doses that do not alter the remaining behavioral repertoire (Fish et al 1999;de Almeida et al 2001;Miczek and de Almeida 2001). At higher 5-HT 1B receptor agonist doses sexual and alimentary behavior is suppressed and motor behavior stimulated (Hillegaart and Ahlenius 1998;Lee et al 1998;Stenfors et al 2000).…”

mentioning

confidence: 99%

Aggression Escalated by Social Instigation or by Discontinuation of Reinforcement (“Frustration”) in Mice Inhibition by Anpirtoline: A 5-HT1B Receptor Agonist

Almeida

2002

Neuropsychopharmacology

138

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Experiments with social instigation or the omission of scheduled reinforcement show that serotonergic mechanisms may be involved in escalated aggression in animals. 5-HT 1B receptor agonists have anti-aggressive effects in individuals who show moderate as well as high levels of aggression. The present study compared the effects of the 5-HT 1B agonist anpirtoline (0.125-1.5 mg/kg) on (1) species-typical aggressive behavior in male mice, (2) aggression "instigated" or primed by prior exposure to the opponent, and (3) aggression heightened by "frustration" caused by omission of scheduled reinforcement. The effects of anpirtoline on species-typical behavior were also assessed after pretreatment with the 5-HT 1B/1D receptor antagonist GR127935 (10 mg/kg). Anpirtoline, like other 5-HT 1Bagonists 253, zolmitriptan) The development of valid experimental protocols that model clinically relevant, excessive levels of aggressive behavior is a continuing challenge for pre-clinical research on aggression (Miczek 2001). The leading neurobiological hypothesis attributes such intense aggressive behavior, often related to expressions of impulsivity, to a deficit in brain serotonin (Linnoila et al. 1983;Virkkunen et al. 1989;Coccaro 1989). An early example of this research strategy was the demonstration that mice would exhibit intense aggressive behavior after prolonged isolated housing, and this isolation-induced aggression is associated with lower serotonin turnover in the brainstem ). Long-standing concerns with the validity and reliability of isolation-induced aggression and its limited species generality prompt the search for alternate approaches (Brain 1975;Krsiak 1975). Similarly, correlation of aggressive behavior with a single tissue or CSF measurement of serotonin or its metabolite need to be reconciled with the anti-aggressive effects of agonist NO . 2 and antagonist treatment of specific serotonin receptor subtypes (Olivier et al. 1995;de Almeida et al. 2001).The exposure of an experimental subject to a potential rival for a short time prior to the actual confrontation engenders intense levels of aggression, as originally described in mice (Lagerspetz 1969;Tellegen and Horn 1972). For example, mice, rats, and hamsters initiate attacks with very short latency and at high frequency when tested with an intruder in their home cage or in an unfamiliar locale after having been provoked previously by an opponent (Potegal 1992;Fish et al. 1999). Instigation or priming is specific for increasing aggressive behavior and does not activate locomotion, feeding, or sexual behavior (Lagerspetz and Hautojarvi 1967;Potegal and Tenbrink 1984;Potegal 1992). Even after removal of the instigating or priming stimulus, high levels of aggression persist in fish and rodents, presumably from increased "aggressive arousal" or "attack readiness" (Heiligenberg 1974;Potegal and Tenbrink 1984;Potegal 1992). At the neurochemical level, animals that have been instigated to fight are characterized by a long-lasting decrease in serotonin in hypoth...

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Oral drug self-administration in the home cage of mice: alcohol-heightened aggression and inhibition by the 5-HT 1B agonist anpirtoline

Cited by 84 publications

References 42 publications

Escalated Aggression after Alcohol Drinking in Male Mice: Dorsal Raphé and Prefrontal Cortex Serotonin and 5-HT1B Receptors

Escalated Aggression after Alcohol Drinking in Male Mice: Dorsal Raphé and Prefrontal Cortex Serotonin and 5-HT1B Receptors

Prevention of Alcohol-Heightened Aggression by CRF-R1 Antagonists in Mice: Critical Role for DRN-PFC Serotonin Pathway

Aggression Escalated by Social Instigation or by Discontinuation of Reinforcement (“Frustration”) in Mice Inhibition by Anpirtoline: A 5-HT1B Receptor Agonist

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