SEROTONERGIC MODULATION OF THE VENTRAL PALLIDUM BY 5HT1A, 5HT5A, 5HT7 AND 5HT2C RECEPTORS

Abstract

Introduction: Serotonin's involvement in reward processing is controversial. The large number of serotonin receptor
sub-types and their individual and unique contributions have been difficult to dissect out, yet understanding how
specific serotonin receptor sub-types contribute to its effects on areas associated with reward processing is an
essential step.
Methods: The current study used multi-electrode arrays and acute slice preparations to examine the effects of
serotonin on ventral pallidum (VP) neurons.
Approach for statistical analysis: extracellular recordings were spike sorted using template matching and principal
components analysis, Consecutive inter-spike intervals were then compared over periods of 1200 seconds for each
treatment condition using a student’s t test.
Results and conclusions: Our data suggests that excitatory responses to serotonin application are pre-synaptic in
origin as blocking synaptic transmission with low-calcium aCSF abolished these responses. Our data also suggests
that 5HT1a, 5HT5a and 5HT7 receptors contribute to this effect, potentially forming an oligomeric complex, as 5HT1a
antagonists completely abolished excitatory responses to serotonin application, while 5HT5a and 5HT7 only reduced
the magnitude of excitatory responses to serotonin. 5HT2c receptors were the only serotonin receptor sub-type
tested that elicited inhibitory responses to serotonin application in the VP. These findings, combined with our
previous data outlining the mechanisms underpinning dopamine's effects in the VP, provide key information, which
will allow future research to fully examine the interplay between serotonin and dopamine in the VP. Investigation of
dopamine and serotonins interaction may provide vital insights into our understanding of the VP's involvement in
reward processing. It may also contribute to our understanding of how drugs of abuse, such as cocaine, may hijack
these mechanisms in the VP resulting in sensitization to drugs of abuse.