bioRxiv Science⌕ Search

Biology subjects

Sniffen, S. E.

Publications and source records attributed to Sniffen, S. E..

2 recordsLinked to original sources

In-dwelling microfluidic device for precise and reliable intranasal drug delivery during freely-moving behavior

Many substances/drugs are administered intranasally (IN). These include opioid overdose reversal drugs, anti-epileptic medications, migraine medications, hormone treatments, and medicines to treat/prevent allergies, colds, and flues including nasally-administered vaccines, corticosteroids, antihistamines, and decongestants. Additionally, IN administration is the preferred route of entry by users of illicit drugs. Despite the widespread use of the IN route of administration, there is no established paradigm to access this route of administration preclinically to yield precise and reliable control over delivery. This poses major gaps in therapeutic discovery/testing, establishing pharmacokinetic/pharmacodynamic relationships of therapeutics, and understanding the mechanisms of actions of therapeutics. We developed an in-dwelling microfluidic device, that, when implanted upon the nasal bone, accesses the nasal cavity to allow reliable and precise IN fluid delivery during freely-moving behavior. We validated this device, called the Nasal Access Port (NAP), to confirm it allows rapid and precise control of fluids. We further exemplified the application of the NAP for studying outcomes of IN cocaine in mice, including its pharmacokinetic profile, and both the rapid release of dopamine (DA) and behavioral effects upon IN cocaine. By achieving precise and reliable access to the IN route of administration, the NAP represents a significant methodological advance with broad applicability in the biomedical and life sciences, especially in the neuroscience, pharmacology, medicinal chemistry, and physiology domains.

pharmacology and toxicology↗

Bidirectional modulation of negative emotional states by parallel genetically-distinct basolateral amygdala pathways to ventral striatum subregions

Distinct basolateral amygdala (BLA) cell populations influence emotional responses in manners thought important for anxiety and anxiety disorders. The BLA contains numerous cell types which can broadcast information into structures that may elicit changes in emotional states and behaviors. BLA excitatory neurons can be divided into two main classes, one of which expresses Ppp1r1b (encoding protein phosphatase 1 regulatory inhibitor subunit 1B) which is downstream of the genes encoding the D1 and D2 dopamine receptors (drd1 and drd2 respectively). The role of drd1+ or drd2+ BLA neurons in learned and unlearned emotional responses is unknown. Here, we identified that the drd1+ and drd2+ BLA neuron populations form two parallel pathways for communication with the ventral striatum. These neurons arise from the basal nucleus of the BLA, innervate the entire space of the ventral striatum, and are capable of exciting ventral striatum neurons. Further, through three separate behavioral assays, we found that the drd1+ and drd2+ parallel pathways bidirectionally influence both learned and unlearned emotional states when they are activated or suppressed, and do so depending upon where they synapse in the ventral striatum - with unique contributions of drd1+ and drd2+ circuitry on negative emotional states. Overall, these results contribute to a model whereby parallel, genetically-distinct BLA to ventral striatum circuits inform emotional states in a projection-specific manner.

neuroscience↗