# Drugs of abuse drive transmitter switching that causes drug-induced behavior

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $196,875

## Abstract

Project Summary Abstract:
Repeated exposure to a drug of abuse can lead to the development of an addiction, a chronic and relapsing
illness that has been defined as the compulsion to seek and take the drug, the loss of control in limiting intake,
and the emergence of a negative emotional state. The transition from drug intake to addiction involves
neuroplasticity of brain circuits related to reward, impulse control and affect. One of the brain regions that is
functionally impaired by drug intake is the prefrontal cortex (PFC), in which drugs of abuse induce alterations in
activity that seem to be crucially involved in the loss of control over drug intake. Increasing our knowledge of
the ways in which drugs of abuse impact these circuits is important to better understand the mechanisms
underlying the transition to addiction and to allow the development of novel interventions and treatment.
The proper function of brain circuits relies on the correct specification and orchestration of neurotransmission.
Accumulating evidence has recently established that when prolonged environmental stimuli produce a
sustained alteration in the electrical activity of a subset of neurons, these neurons can undergo a
respecification of the neurotransmitter they express, often resulting in a switch from an excitatory to an
inhibitory transmitter or vice versa. This newly appreciated form of neuroplasticity, called neurotransmitter
switching, has been repeatedly observed in the adult mammalian brain and associated with alterations in
animal behavior.
We hypothesize that repeated exposure to drugs of abuse can induce neurotransmitter switching that in turn
contributes to the establishment of drug-induced behavioral alterations such as cognitive deficits, behavioral
sensitization and drug-induced reinforcement. Two specific aims will test this hypothesis. The 1st specific aim
will test whether sub-chronic treatment with PCP or METH induces neurotransmitter switching in the PFC. The
2nd specific aim will determine whether there is a causal link between neurotransmitter switching and drug-
induced behavioral alterations including cognitive deficits, behavioral sensitization, and drug-induced
reinforcement.

## Key facts

- **NIH application ID:** 9982842
- **Project number:** 5R21DA048633-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** NICHOLAS CANADAY SPITZER
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $196,875
- **Award type:** 5
- **Project period:** 2019-08-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9982842

## Citation

> US National Institutes of Health, RePORTER application 9982842, Drugs of abuse drive transmitter switching that causes drug-induced behavior (5R21DA048633-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9982842. Licensed CC0.

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