Abstract

It's widely known that all addictive drugs show analogous pathological behaviours consisting in compulsive drug seeking,loss of self –control and propensity to relapse. This evidence is suggestive of a common brain mechanism involving the Ventral Tegmental Area and Nucleus Accumbens whereby mesocorticolimbimc dopamine pathway. Dfferent and apparently anthitetic classes of drugs of abuse manage to increase DA release, in the aforementioned areas (Di Chiara,1988; 1995). Reductions in activity of the mesolimbic dopamine system in the nucleus accumbes occur during drugwithdrawal in animal studies (Weiss F et al. 1992; 1996).Experimental evidences have proven D2 receptor involvement in drug seeking and reinstatement behaviours. In that,according to the hypo-dopaminergic hypothesis of drug abuse, striatal D2-receptors significantly decrease during forcedabstinence (Thanos, 2008). These premises suggest that D2 receptor manipulations might represent a valid strategy foralcohol dependence.Ropinirole, a D2-D3 receptors agonist, apparently acting on post-synaptical terminal and thus previously administered inmethamphetamine withdrawal (Hoefer, 2006), could reduce drug intake in the reinstatement by means of its presumableproperties in compensating DA reduction during abstinence. Acetaldehyde, alcohol first metabolite, is able to induce andmaintain an operantdrinking behaviour, because of its addictive properties (Cacace, 2012).This research pointed at evaluating Ropinirole protective effect on ACD relapse as a possible therapeutic tool, togetherwith a dose-response investigation.Rats were trained to self-administer ACD 3,2% solution along 30 days. Then, animals underwent three cycles, each oneconsisting of withdrawal (7days) followed by relapse phase (5 days). The first withdrawal-relapse cycle provided basalinformation of animal responses for ACD. During the second withdrawal phase, rats were treated i.p. daily with Ropiniroleunder the dosage of 0.03mg/kg. A third cycle of withdrawal and relapse was performed so as to correlate the drug potencyto a higher dosage of 0.05mg/kg. Preliminary data convey that the aforementioned DA agonist is able to reduce animalresponses for ACD also at the latter dosage, which is proved by a lower frequency of lever presses during the third relapsephase.An open field test was used to exclude a not specific Ropinirole effect on reducing locomotor activity and to assessdopaminergic activation by measuring the number of episodes of stereotypes, such as grooming and rearing. Our resultsindicated that this DA agonist, administered during withdrawal phase, is able to limit ACD reinstatement with responses dose-related. Such studies may be implemented in order to assess Ropinirole efficacy in other drug addictions, starting with alcoholism investigations
Lingua originaleEnglish
Numero di pagine1
Stato di pubblicazionePublished - 2013

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Recurrence
Pharmaceutical Preparations
Substance-Related Disorders
Dopamine
Tegmentum Mesencephali
Drug-Seeking Behavior
Corpus Striatum
Grooming
Dopamine Agents
Ventral Tegmental Area
Acetaldehyde
Nucleus Accumbens
Street Drugs
Locomotion
Alcoholism
Alcohols
ropinirole
Brain
Research
Therapeutics

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@conference{8182d04b31834852a80081c89b08df96,
title = "Manipulation of the DA signal on the onset of relapse of ACD",
abstract = "It's widely known that all addictive drugs show analogous pathological behaviours consisting in compulsive drug seeking,loss of self –control and propensity to relapse. This evidence is suggestive of a common brain mechanism involving the Ventral Tegmental Area and Nucleus Accumbens whereby mesocorticolimbimc dopamine pathway. Dfferent and apparently anthitetic classes of drugs of abuse manage to increase DA release, in the aforementioned areas (Di Chiara,1988; 1995). Reductions in activity of the mesolimbic dopamine system in the nucleus accumbes occur during drugwithdrawal in animal studies (Weiss F et al. 1992; 1996).Experimental evidences have proven D2 receptor involvement in drug seeking and reinstatement behaviours. In that,according to the hypo-dopaminergic hypothesis of drug abuse, striatal D2-receptors significantly decrease during forcedabstinence (Thanos, 2008). These premises suggest that D2 receptor manipulations might represent a valid strategy foralcohol dependence.Ropinirole, a D2-D3 receptors agonist, apparently acting on post-synaptical terminal and thus previously administered inmethamphetamine withdrawal (Hoefer, 2006), could reduce drug intake in the reinstatement by means of its presumableproperties in compensating DA reduction during abstinence. Acetaldehyde, alcohol first metabolite, is able to induce andmaintain an operantdrinking behaviour, because of its addictive properties (Cacace, 2012).This research pointed at evaluating Ropinirole protective effect on ACD relapse as a possible therapeutic tool, togetherwith a dose-response investigation.Rats were trained to self-administer ACD 3,2{\%} solution along 30 days. Then, animals underwent three cycles, each oneconsisting of withdrawal (7days) followed by relapse phase (5 days). The first withdrawal-relapse cycle provided basalinformation of animal responses for ACD. During the second withdrawal phase, rats were treated i.p. daily with Ropiniroleunder the dosage of 0.03mg/kg. A third cycle of withdrawal and relapse was performed so as to correlate the drug potencyto a higher dosage of 0.05mg/kg. Preliminary data convey that the aforementioned DA agonist is able to reduce animalresponses for ACD also at the latter dosage, which is proved by a lower frequency of lever presses during the third relapsephase.An open field test was used to exclude a not specific Ropinirole effect on reducing locomotor activity and to assessdopaminergic activation by measuring the number of episodes of stereotypes, such as grooming and rearing. Our resultsindicated that this DA agonist, administered during withdrawal phase, is able to limit ACD reinstatement with responses dose-related. Such studies may be implemented in order to assess Ropinirole efficacy in other drug addictions, starting with alcoholism investigations",
author = "Carla Cannizzaro and Anna Brancato and Fulvio Plescia and Marino, {Rosa Anna Maria}",
year = "2013",
language = "English",

}

TY - CONF

T1 - Manipulation of the DA signal on the onset of relapse of ACD

AU - Cannizzaro, Carla

AU - Brancato, Anna

AU - Plescia, Fulvio

AU - Marino, Rosa Anna Maria

PY - 2013

Y1 - 2013

N2 - It's widely known that all addictive drugs show analogous pathological behaviours consisting in compulsive drug seeking,loss of self –control and propensity to relapse. This evidence is suggestive of a common brain mechanism involving the Ventral Tegmental Area and Nucleus Accumbens whereby mesocorticolimbimc dopamine pathway. Dfferent and apparently anthitetic classes of drugs of abuse manage to increase DA release, in the aforementioned areas (Di Chiara,1988; 1995). Reductions in activity of the mesolimbic dopamine system in the nucleus accumbes occur during drugwithdrawal in animal studies (Weiss F et al. 1992; 1996).Experimental evidences have proven D2 receptor involvement in drug seeking and reinstatement behaviours. In that,according to the hypo-dopaminergic hypothesis of drug abuse, striatal D2-receptors significantly decrease during forcedabstinence (Thanos, 2008). These premises suggest that D2 receptor manipulations might represent a valid strategy foralcohol dependence.Ropinirole, a D2-D3 receptors agonist, apparently acting on post-synaptical terminal and thus previously administered inmethamphetamine withdrawal (Hoefer, 2006), could reduce drug intake in the reinstatement by means of its presumableproperties in compensating DA reduction during abstinence. Acetaldehyde, alcohol first metabolite, is able to induce andmaintain an operantdrinking behaviour, because of its addictive properties (Cacace, 2012).This research pointed at evaluating Ropinirole protective effect on ACD relapse as a possible therapeutic tool, togetherwith a dose-response investigation.Rats were trained to self-administer ACD 3,2% solution along 30 days. Then, animals underwent three cycles, each oneconsisting of withdrawal (7days) followed by relapse phase (5 days). The first withdrawal-relapse cycle provided basalinformation of animal responses for ACD. During the second withdrawal phase, rats were treated i.p. daily with Ropiniroleunder the dosage of 0.03mg/kg. A third cycle of withdrawal and relapse was performed so as to correlate the drug potencyto a higher dosage of 0.05mg/kg. Preliminary data convey that the aforementioned DA agonist is able to reduce animalresponses for ACD also at the latter dosage, which is proved by a lower frequency of lever presses during the third relapsephase.An open field test was used to exclude a not specific Ropinirole effect on reducing locomotor activity and to assessdopaminergic activation by measuring the number of episodes of stereotypes, such as grooming and rearing. Our resultsindicated that this DA agonist, administered during withdrawal phase, is able to limit ACD reinstatement with responses dose-related. Such studies may be implemented in order to assess Ropinirole efficacy in other drug addictions, starting with alcoholism investigations

AB - It's widely known that all addictive drugs show analogous pathological behaviours consisting in compulsive drug seeking,loss of self –control and propensity to relapse. This evidence is suggestive of a common brain mechanism involving the Ventral Tegmental Area and Nucleus Accumbens whereby mesocorticolimbimc dopamine pathway. Dfferent and apparently anthitetic classes of drugs of abuse manage to increase DA release, in the aforementioned areas (Di Chiara,1988; 1995). Reductions in activity of the mesolimbic dopamine system in the nucleus accumbes occur during drugwithdrawal in animal studies (Weiss F et al. 1992; 1996).Experimental evidences have proven D2 receptor involvement in drug seeking and reinstatement behaviours. In that,according to the hypo-dopaminergic hypothesis of drug abuse, striatal D2-receptors significantly decrease during forcedabstinence (Thanos, 2008). These premises suggest that D2 receptor manipulations might represent a valid strategy foralcohol dependence.Ropinirole, a D2-D3 receptors agonist, apparently acting on post-synaptical terminal and thus previously administered inmethamphetamine withdrawal (Hoefer, 2006), could reduce drug intake in the reinstatement by means of its presumableproperties in compensating DA reduction during abstinence. Acetaldehyde, alcohol first metabolite, is able to induce andmaintain an operantdrinking behaviour, because of its addictive properties (Cacace, 2012).This research pointed at evaluating Ropinirole protective effect on ACD relapse as a possible therapeutic tool, togetherwith a dose-response investigation.Rats were trained to self-administer ACD 3,2% solution along 30 days. Then, animals underwent three cycles, each oneconsisting of withdrawal (7days) followed by relapse phase (5 days). The first withdrawal-relapse cycle provided basalinformation of animal responses for ACD. During the second withdrawal phase, rats were treated i.p. daily with Ropiniroleunder the dosage of 0.03mg/kg. A third cycle of withdrawal and relapse was performed so as to correlate the drug potencyto a higher dosage of 0.05mg/kg. Preliminary data convey that the aforementioned DA agonist is able to reduce animalresponses for ACD also at the latter dosage, which is proved by a lower frequency of lever presses during the third relapsephase.An open field test was used to exclude a not specific Ropinirole effect on reducing locomotor activity and to assessdopaminergic activation by measuring the number of episodes of stereotypes, such as grooming and rearing. Our resultsindicated that this DA agonist, administered during withdrawal phase, is able to limit ACD reinstatement with responses dose-related. Such studies may be implemented in order to assess Ropinirole efficacy in other drug addictions, starting with alcoholism investigations

UR - http://hdl.handle.net/10447/84906

M3 - Other

ER -