The brain’s tubular striatum (TuS, also known as the olfactory tubercle) receives both monosynaptic input from the olfactory bulb and midbrain dopaminergic input, which uniquely positions it to influence odor-guided motivated behaviors and odor hedonics. Furthermore, the TuS has abundant expression of aromatase, allowing for local, de novo synthesis of 17β-estradiol (E2). Given local E2’s ability to rapidly influence neural activity and the established role of the TuS in odor valence, we reasoned that E2 in the TuS may influence attraction to odors. Using plethysmography, we examined odor-evoked high-frequency sniffing as a measure of odor attraction. Bilateral infusion of the aromatase inhibitor letrozole into the TuS of gonadectomized female adult mice induced a resistance to habituation over successive trials in their investigatory sniffing for female mouse urinary odor. Therefore, E2 in the TuS impacts attraction to ethologically relevant odors. We next sought to determine the role of TuS dopamine (DA) in odor-guided behaviors. Using in vivo fiber photometry and the DA sensor GRABDA, we observed a relationship between high frequency sniff bouts and DA release in the TuS. Since the TuS is largely comprised of neurons that express either DA 1 (D1) or DA 2 (D2) receptors, we then bilaterally infused either a D1 or D2 receptor antagonist, SCH23390 or raclopride, respectively, into the TuS of gonadally-intact mice. We found that inhibition of both D1 and D2 receptors reduced bouts of exploratory sniffing. Furthermore, inhibition of D2 receptors reduced investigatory sniffing to innately attractive odors. These data suggest that DA’s actions in the TuS also impact behavior toward attractive odors. Because E2 can affect brain DA, including enhancement of DAergic transmission, ongoing work aims to explore the combined role of E2 and DA in odor-guided behaviors.

Funding: NIDCD F31 DC020364, NIDCD F32 DC018452, NIDA R01 DA049545, NIDA R01 DA049449, NINDS R01 NS117061