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Neurobiological Consequences of Social Conditions and Alcohol Exposure in Adolescent rats
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (Neurofarmakologi, bereoende och beteende)
2015 (English)Licentiate thesis, comprehensive summary (Other academic)
Abstract [en]

Adolescence represents a time of extensive reorganisation and maturation of brain circuits involved in emotions, motivation and cognition and it is a period particular sensitive for external stimuli. External stimuli can be both socio-environmental factors and exposure to exogenous compounds such as drugs of abuse (e.g. alcohol). If these stimuli are of an adverse nature the probability of develop neuropsychiatric diseases or addiction is increased. To study the neurobiological consequences of adverse events during adolescence animal models are crucial since they give the opportunity of providing an environment where the exposure of the stimuli is controlled and also enable a detailed analysis of the effects in the brain. The overall aim of in this thesis was to investigate how environmental factors, social conditions or alcohol exposure, during adolescence affect the brain and/or drug-taking in rats. Rats are very sensitive for dis- turbances in their social conditions and to induce an adverse social environment, early adolescent rats where single-housed for either a short or prolonged time. A short period of single housing induced an acute stress response and increased levels of nociceptin/orphanin FQ in brain areas associated with stress. Prolonged single housing reduced the levels of Met-enkephalin-Arg6Phe7 in several brain areas. Rats exposed to alcohol during adolescence had an altered dopamine response in dorsal striatum after an am- phetamine challenge but displayed similar amphetamine intake-behaviour as water controls. However, animals exposed to a combination of adolescent alcohol exposure and subsequent amphetamine intake had a more efficient removal of dopamine in dorsal striatum after an amphetamine challenge. This thesis demonstrates how two different environmental stimuli are able to alter the neurobiology in adolescent rats. The results further support the notion that environmental conditions are of importance for normal brain maturation and provide new evidence that endogenous opioids are severely affected by social dis- turbances during adolescence. Furthermore, additional information is provided to the existing literature of how alcohol exposure during adolescence affects dopamine dynamics and drug-taking behaviour. In the literature, the majority of the studies of adolescent alcohol exposure have focused on the nucleus accum- bens, a brain area important in the processing of rewards. The results herein provide evidence that dorsal striatum, a brain area involved in the transition into habitual drug use is also affected by adolescent alco- hol exposure. An altered drug response in dorsal striatum may affect habit formation and contribute to a heightened susceptibility for high drug consumption later in life.

Place, publisher, year, edition, pages
Uppsala University, 2015.
Series
, Faculty of Pharmacy, Uppsala University Licentiate Theses, 48
Keyword [en]
adolescence, alcohol, amphetamine, dopamine, dorsal striatum, dynorphin, endogenous opi- oids, enkephalin, high-speed chronoamperometry, housing conditions, rats, nociceptin/orphanin FQ, radi- oimmunoassay, self-administration
National Category
Neurosciences
Research subject
Pharmaceutical Science
Identifiers
URN: urn:nbn:se:uu:diva-291416OAI: oai:DiVA.org:uu-291416DiVA: diva2:925505
Supervisors
Available from: 2016-05-03 Created: 2016-05-02 Last updated: 2016-05-03Bibliographically approved
List of papers
1. Single housing during early adolescence causes time-, area- and peptide-specific alterations in endogenous opioids of rat brain
Open this publication in new window or tab >>Single housing during early adolescence causes time-, area- and peptide-specific alterations in endogenous opioids of rat brain
2015 (English)In: British Journal of Pharmacology, ISSN 0007-1188, E-ISSN 1476-5381, Vol. 172, no 2, 606-614 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND AND PURPOSE: A number of experimental procedures require single housing to assess individual behaviour and physiological responses to pharmacological treatments. The endogenous opioids are closely linked to social interaction, especially early in life, and disturbance in the social environment may affect opioid peptides and thereby confound experimental outcome. The aim of the present study was to examine time-dependent effects of single housing on opioid peptides in rats.

EXPERIMENTAL APPROACH: Early adolescent Sprague Dawley rats (post-natal day 22) were subjected to either prolonged (7 days) or short (30 min) single housing. Several brain regions were dissected and immunoreactive levels of Met-enkephalin-Arg(6) Phe(7) (MEAP), dynorphin B and nociception/orphanin FQ, as well as serum corticosterone were measured using RIA.

KEY RESULTS: Prolonged single housing reduced immunoreactive MEAP in hypothalamus, cortical regions, amygdala, substantia nigra and periaqueductal grey. Short single housing resulted in an acute stress response as indicated by high levels of corticosterone, accompanied by elevated immunoreactive nociceptin/orphanin FQ in medial prefrontal cortex, nucleus accumbens and amygdala. Neither short nor prolonged single housing affected dynorphin B.

CONCLUSIONS AND IMPLICATIONS: Disruption in social environmental conditions of rats, through single housing during early adolescence, resulted in time-, area- and peptide-specific alterations in endogenous opioids in the brain. These results provide further evidence for an association between early life social environment and opioids. Furthermore, the results have implications for experimental design; in any pharmacological study involving opioid peptides, it is important to distinguish between effects induced by housing and treatment.

National Category
Neurosciences Pharmaceutical Sciences
Identifiers
urn:nbn:se:uu:diva-241312 (URN)10.1111/bph.12753 (DOI)000346826500032 ()24821004 (PubMedID)
Available from: 2015-01-09 Created: 2015-01-09 Last updated: 2016-05-03Bibliographically approved
2. Impact of adolescent ethanol exposure and adult amphetamine self-administration on evoked striatal dopamine release in male rats
Open this publication in new window or tab >>Impact of adolescent ethanol exposure and adult amphetamine self-administration on evoked striatal dopamine release in male rats
Show others...
2015 (English)In: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 232, no 24, 4421-4431 p.Article in journal (Refereed) Published
Abstract [en]

Adolescent binge drinking is common and associated with increased risk of substance use disorders. Transition from recreational to habitual ethanol consumption involves alterations in dorsal striatal function, but the long-term impact of adolescent ethanol exposure upon this region remains unclear. This study aimed to characterise and describe relationships between adolescent ethanol exposure, amphetamine self-administration and adult dopamine dynamics in dorsal striatum, including response to amphetamine challenge, in male Wistar rats. Ethanol (2 g/kg) or water was administered intragastrically in an episodic binge-like regimen (three continuous days/week) between 4 and 9 weeks of age (i.e. post-natal days 28-59). In adulthood, animals were divided into two groups. In the first, dorsal striatal potassium-evoked dopamine release was examined via chronoamperometry, in the basal state and after a single amphetamine challenge (2 mg/kg, i.v.). In the second, amphetamine self-administration behaviour was studied (i.e. fixed and progressive ratio) before chronoamperometric analysis was conducted as described above. Adolescent ethanol exposure suppressed locally evoked dopamine response after amphetamine challenge in adulthood, whereas in the basal state, no differences in dopamine dynamics were detected. Ethanol-exposed animals showed no differences in adult amphetamine self-administration behaviour but an abolished effect on dopamine removal in response to a single amphetamine challenge after self-administration. Amphetamine challenges in adult rats revealed differences in in vivo dopamine function after adolescent ethanol exposure. The attenuated drug response in ethanol-exposed animals may affect habit formation and contribute to increased risk for substance use disorders as a consequence of adolescent ethanol.

Keyword
Chronoamperometry, Operant self-administration, Alcohol, Rodents
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-270438 (URN)10.1007/s00213-015-4070-3 (DOI)000365186600004 ()26407601 (PubMedID)
Funder
Swedish Research Council, K2012-61X-22090-01-3
Available from: 2016-02-08 Created: 2015-12-28 Last updated: 2016-05-03Bibliographically approved

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