The potential effect of rosmarin acid on the prevention and treatment of chemical dependence on cocaine in mice: a study behavioral and molecular
Name: TAYNARA GABRIELE CAMPOS
Type: MSc dissertation
Publication date: 17/02/2022
Advisor:
Name |
Role |
|---|---|
| RITA GOMES WANDERLEY PIRES | Advisor * |
Examining board:
| Name |
Role |
|---|---|
| ALICE LASCHUK HERLINGER | Co advisor * |
| JULIANA BARBOSA COITINHO GONCALVES | Internal Examiner * |
| RITA GOMES WANDERLEY PIRES | Advisor * |
Summary: Cocaine is an illegal drug that presents itself as a serious social and public health problem. Cocaine acts by blocking dopaminergic transporters (DATs) that are responsible for the reuptake of dopamine (DA) released in the synaptic cleft. With its activity inhibited, DA accumulates in the cleft, increasing dopaminergic signaling in the Central Nervous System (CNS). In the CNS, dopaminergic neurons are located in the Ventral Tegmental Area (VTA), projecting to the Nucleus Accumbens (NAc) and the Prefrontal Cortex (PFC), composing the mesolimbic pathway. This pathway is responsible for the brain encoding of reward evaluation, behavior and decision-making processes. Today there is no effective treatment for cocaine addiction. In cases of dependence, the only action is abstinence. Thus, there is a need to study new drugs for this purpose, since abstinence brings together a series of side effects such as vomiting, fever and depression. Rosmarinic acid (AR), a compound derived from spices such as rosemary, sage, basil, among others; has shown a key role as an antioxidant, anti-inflammatory and neuroprotective. Thus, the present study aimed to link the actions already observed in RA as a proposal for a drug for cocaine addiction. We used an animal model with male C57BL/6 mice that received cocaine for five days. After the drug dependence induction step, the animals were left for five days in abstinence and a relapse model was made from drug re-exposure.The pharmaceutical potential of RA was analyzed in three different contexts: a pre-treatment, a constant treatment and a treatment only during abstinence. The behavioral effects from the open field test and the biochemical scope were analyzed with evaluation of the gene expression of addition markers (CREB, BDNF and △FosB) in the CPF region by qRT-PCR. An attenuation in the increase in locomotor activity was identified in all AR-treated groups. A positive effect with respect to the first exposure was seen in the pre-treated groups. However, the AR demonstrated a temporary effect seen by the behavior of the group that received the compound only in the pre-treatment when related to the control group. As for re-exposure, the group treated continuously showed lower locomotor activity compared to the others, showing drug resistance in a relapse scenario. The biochemical profile showed no change in CREB expression. A differential profile was identified in the animals treated with RA during abstinence with the effects of cocaine on the day of challenge, showing an increase in the expression of △FosB and BDNF in these groups. AR has shown good potential to be used as a drug for cocaine addiction, but molecular studies must be further explored and, additionally, AR must be tested within the scope of protocols that use the voluntary search for the drug.
Keywords: cocaine, AR, prefrontal cortex, dopaminergic system, locomotor activity, addiction markers.
