Institutional creator:

Instytut Biologii Doświadczalnej im. Marcelego Nenckiego PAN

Contributor:

Hamed, Adan : Supervisor ; Kursa, Miron : Auxiliary supervisor

Publisher:

Instytut Biologii Doświadczalnej im. Marcelego Nenckiego PAN

Place of publishing:

Warszawa

Description:

230 pages, [2] folded cards : ilustrations ; 30 cm ; Bibliography ; Summary in English

Degree name:

PhD in Biological Sciences

Degree discipline :

Biological Sciences

Degree grantor:

Nencki Institute of Experimental Biology PAS ; degree obtained: 27.06.2025

Type of object:

Thesis

Abstract:

Drug craving is an intense desire or need to engage in specific behaviors related to psychoactive substance use. The phenomenon known as incubation of craving is characterized by a gradual increase in the intensity of craving symptoms over time, which increases the likelihood of relapse triggered by spatial cues associated with substance intake. Previous research has shown that re-exposure to a morphine-paired context after withdrawal elicits increased “50-kHz” ultrasonic vocalizations (USVs) in rats, which are interpreted as markers of positive affective states. This study investigated the role of serotonergic and glutamatergic co-transmission in the amygdala in modulating drug-paired context-induced behavioral responses after withdrawal. The amygdala is a brain structure involved in emotional responses to both aversive and appetitive stimuli. A classical animal model of place conditioning and a DREADD chemogenetic technique (using hM3Dq and/or hM4Di receptors) to manipulate the activity of the serotonergic and glutamatergic neurons in the amygdala, were employed. The impact of these chemogenetic manipulations on the number of ultrasonic vocalizations emitted and the distance travelled by rats during the context response was assessed. Additionally, the effects of these manipulations on levels of monoamines, their metabolites, amino acids, and neuromodulators in selected brain structures were investigated, along with the relationships between the neurochemical systems and their association with behavioral changes. This study demonstrated a significant role of serotonergic-glutamatergic co- transmission in the amygdala in shaping the drug-paired context-induced response. No strong correlation was found between the number of ultrasonic vocalizations and the distance traveled by rats, suggesting that these measures may reflect different aspects of the context response (USV – emotional, while distance – motivational). A significant effect of the chemogenetic modifications on the number of ultrasonic vocalizations in the context response test was observed: a statistically significant reduction in the number of USVs in the "5-HT-" (inhibition of serotonergic signaling) and "Glu+5-HT-" (simultaneous activation of glutamatergic signaling and inhibition of serotonergic signaling) groups and increase in the "Glu+5-HT+" (simultaneous activation of glutamatergic and serotonergic signaling) group. Moreover, the study revealed a complex network of neurochemical associations and correlations. Further analysis revealed a diverse neurochemical basis for the expression of the affective state, confirming that the same behavioral effect can result from the activity of a number of distinct neurotransmitter system networks. This experiment highlighted the complexity of the neurobiological basis of addiction, emphasizing the need for a holistic approach in studying this phenomenon.

Detailed Resource Type:

PhD Dissertations

Resource Identifier:

oai:rcin.org.pl:245092

Source:

IBD PAN, call no. 20764

Language:

pol

Language of abstract:

eng

Rights:

Rights Reserved - Free Access

Terms of use:

Copyright-protected material. May be used within the limits of statutory user freedoms

Copyright holder:

Publication made available with the written permission of the author

Digitizing institution:

Nencki Institute of Experimental Biology of the Polish Academy of Sciences

Original in:

Library of the Nencki Institute of Experimental Biology PAS

Access:

Open