Dopamine D2-like receptors on conditioned and unconditioned fear: A systematic review of rodent pharmacological studies

Author(s)

de Oliveira Alves, Camila ; Waku, Isabelle ; Chiossi, Joyce Nonato ; de Oliveira, Amanda Ribeiro

• Document type: Journal article
• Source: PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY; v. 134, p. 20-pg., 2024-07-02.

Abstract

Growing evidence supports dopamine's role in aversive states, yet systematic reviews focusing on dopamine receptors in defensive behaviors are lacking. This study presents a systematic review of the literature examining the influence of drugs acting on dopamine D2-like receptors on unconditioned and conditioned fear in rodents. The review reveals a predominant use of adult male rats in the studies, with limited inclusion of female rodents. Commonly employed tests include the elevated plus maze and auditory-cued fear conditioning. The findings indicate that systemic administration of D2-like drugs has a notable impact on both innate and learned aversive states. Generally, antagonists tend to increase unconditioned fear, while agonists decrease it. Moreover, both agonists and antagonists typically reduce conditioned fear. These effects are attributed to the involvement of distinct neural circuits in these states. The observed increase in unconditioned fear induced by D2-like antagonists aligns with dopamine's role in suppressing midbrain-mediated responses. Conversely, the reduction in conditioned fear is likely a result of blocking dopamine activity in the mesolimbic pathway. The study highlights the need for future research to delve into sex differences, explore alternative testing paradigms, and identify specific neural substrates. Such investigations have the potential to advance our understanding of the neurobiology of aversive states and enhance the therapeutic application of dopaminergic agents. (AU)

• FAPESP's process: 21/05022-9 - Effects of deep brain stimulation of the ventral capsule/ventral striatum and of the subtalamic nucleus on the performance of rats in behavioral flexibility tasks.
• Grantee: Isabelle Waku
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 21/04949-1 - Involvement of D2-like dopaminergic receptors of the inferior colliculus and basolateral amygdala in the expression of conditioned and unconditioned fear in male and female rats
• Grantee: Camila de Oliveira Alves
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 22/02986-0 - Involvement of dopaminergic mechanisms in conditioned and unconditioned fear: modulation by hormonal factors
• Grantee: Amanda Ribeiro de Oliveira
• Support Opportunities: Research Grants - Initial Project