Biology subjects

Reichel, C. M.

Publications and source records attributed to Reichel, C. M..

4 recordsLinked to original sources

bioRxiv2022

Matrix Metalloproteinase Activity During Methamphetamine Cued Relapse

Relapse to drug seeking involves transient synaptic remodeling that occurs in response to drug associated cues. This remodeling includes activation of matrix metalloproteinases (MMPs) to initiate catalytic signaling in the extracellular matrix (ECM) in the nucleus accumbens core (NAcore). We hypothesized that MMP activity would be increased in the NAcore during cue-induced methamphetamine (meth) seeking in a rat model of meth use and relapse. Male and female rats had indwelling jugular catheters and bilateral intracranial cannula targeting the NAcore surgically implanted. Following recovery, rats underwent meth or saline self-administration (6hr/day for 15 days) in which active lever responding was paired with a light+tone stimulus complex, followed by home cage abstinence. Testing occurred after 7 or 30 days of abstinence. On test day, rats were microinjected with a FITC-quenched gelatin substrate that fluoresces following cleavage by MMPs, allowing for the quantification of gelatinase activity by MMP-2 and -9 during cued relapse testing. MMP-2,9 activity was significantly increased in the NAcore by meth cues presentation after 7 and 30 days of abstinence, indicating that remodeling by MMPs occurs during presentation of meth associated cues. Surprisingly, while cue-induced seeking increased between days 7 and 30, suggesting behavioral incubation, MMP-2,9 activity did not increase. These findings indicate that while MMP activation is elicited during meth cue-induced seeking, MMP activation did not parallel the behavioral incubation that occurs during extended drug abstinence.

neuroscience↗

bioRxiv2022

Neuronal, Affective, and Sensory Correlates of Targeted Helping Behavior in Male and Female Sprague Dawley Rats

Empathy is an innate ability to understand the emotional states of others along with the motivation to improve it. It has evolved over time into highly complex behaviors, the basis of which can be described using the Perception Action Model (PAM), where shared affect promotes an action that eliminates the distress of both the passive "Target" and, by extension, the active "Observer." There are myriad biological variables that may modulate empathic behavior, including sex, sensory modalities, and neural activity. In the following studies, using our labs model of social contact-independent targeted helping, we first tested whether sex differences exist in helping behavior. Next, we explored sex differences in sensory and affective signaling, including the impact of direct visualization of a distressed conspecific and the type of ultrasonic vocalizations (USV) made between animal pairs during the task. Finally, we examined the neural activity of multiple cortical and subcortical regions of interest across time during targeted helping between males and females. We show both sexes exhibit similar helping behavior, but sensory and affective signaling differs between sexes. Further, changes in neural activity exhibited distinct sex-specific patterns across time. Our results indicate sex differences are not a ubiquitous presence in targeted helping. Instead, it is likely sex differences may be a convergent phenomenon in which the behavior is similar, but the underlying biological mechanisms are distinct. These results lay the groundwork for future studies to explore the similarities and differences that drive empathic behavior in both males and females.

animal behavior and cognition↗

bioRxiv2021

Chemogenetic Inhibition of Corticostriatal Circuits Reduces Cued Reinstatement of Methamphetamine Seeking

Methamphetamine (meth) causes enduring changes within the medial prefrontal cortex (mPFC) and the nucleus accumbens (NA). Projections from the mPFC to the NA have a distinct dorsal-ventral distribution, with the prelimbic (PL) mPFC projecting to the NAcore, and the infralimbic (IL) mPFC projecting to the NAshell. Inhibition of these circuits has opposing effects on cocaine relapse. Inhibition of PL-NAcore reduces cued reinstatement of cocaine seeking and IL-NAshell inhibition reinstates cocaine seeking. Meth, however, exhibits a different profile, as pharmacological inhibition of either the PL or IL decrease cued reinstatement of meth-seeking. The potentially opposing roles of the PL-NAcore and IL-NAshell projections remain to be explored in the context of cued meth seeking. Here we used an intersectional viral vector approach that employs a retrograde delivery of Cre from the NA and Cre-dependent expression of DREADD in the mPFC, in both male and female rats to inhibit or activate these parallel pathways. Inhibition of the PL-NAcore circuit reduced cued reinstatement of meth seeking under short and long-access meth self-administration and after withdrawal with and without extinction. Inhibition of the IL-NAshell also decreased meth cued reinstatement. Activation of the parallel circuits was without an effect. These studies show that inhibition of the PL-NAcore or the IL-NAshell circuits can inhibit reinstated meth seeking. Thus, the neural circuitry mediating cued reinstatement of meth seeking is similar to cocaine in the dorsal, but not ventral, mPFC-NA circuit.

neuroscience↗

bioRxiv2021

Effects of high dosage methamphetamine on glutamatergic neurotransmission in the nucleus accumbens and prefrontal cortex.

RationaleMethamphetamine (METH) induces changes in the glutamatergic system and elicits cellular alterations in the cortico-accumbens circuit. ObjectiveWhile there is a body of literature on the effects of METH on dopaminergic transmission, there is a gap in knowledge regarding the effects of a high dose of METH on synaptic glutamatergic neurotransmission, specifically in brain regions involved in goal directed behavior (nucleus accumbens core; NAc core) and executive functions (prefrontal cortex;PFC). MethodsIn order to fill that gap we assessed synaptic glutamatergic transmission using a well established METH administration regime (4 x 4 mg/kg ip at 2 hr intervals) followed by 7 days of abstinence. Rats were then sacrificed and whole cell and field recordings were performed in the NAc core and medial PFC. ResultsMETH treatment elicited a significant decrease in paired pulse ratio in NAc core and a significant increase in AMPA/NMDA ratio driven by increases in AMPA currents. On the other hand, there were no significant changes in measures of synaptic glutamate in the PFC. ConclusionThese results suggest that a high dose of METH treatment followed by a period of abstinence elicits significant increases in indices of glutamatergic transmission in the NAc core with no detectable changes in mPFC, denoting that neurons and glutamate terminals in this limbic region have a higher susceptibility to a neurotoxic METH regime.

neuroscience↗