Fullerton E (2022) The impact of advanced age on morphine anti-hyperalgesia and the role of mu opioid receptor signaling in the periaqueductal gray of male and female rats. Georgia State University doi: 10.57709/30509896

Objective: To investigate the impact of advanced age on the antihyperalgesic effect of morphine, as well as its association with changes in μ-opioid receptor expression and binding in the rat midbrain Periaqueductal Gray (PAG) in both male and female rats.

Summary: This study examined the effects of advanced age on the antihyperalgesic properties of morphine and its relationship with mu-opioid receptor expression and binding in the rat midbrain Periaqueductal Gray (PAG). The findings revealed that advanced age attenuated the antihyperalgesic effect of morphine, accompanied by a decrease in mu-opioid receptor expression and binding in the PAG of both male and female rats, suggesting age-related alterations in opioid signaling that may contribute to reduced analgesic efficacy in older individuals.

Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12)

Q: What are neuropeptide-toxins and how do they work?

A: Neuropeptide-toxin conjugates are made up of the ribosome-inactivating protein, saporin, coupled to a naturally-occurring or synthetically-modified neuropeptide such as Substance P or dermorphin. The conjugate has binding specificity similar to the native, unconjugated neuropeptide. When the neuropeptide binds to its cognate receptor, the conjugate is internalized. Once inside the target cell within an endosome, the neuropeptide and saporin separate and some of the saporin translocates into the cytoplasm where it catalytically inactivates ribosomes resulting in cell death.

Q: Are neuropeptide-toxins effective suicide transport agents?

A: The general answer to this question is not currently known. However, in the instance of intrathecally injected dermorphin-SAP (Cat. #IT-12), the evidence does NOT favor suicide transport of the neuropeptide-toxin conjugate. When supramaximal doses of dermorphin-SAP (750 ng) are injected into the lumbar subarachnoid space of adult rats, less than 1% of lumbar dorsal root ganglion cells show evidence of saporin activity. This is in spite of the fact that many of these neurons express the targeted mu opioid receptor on their central terminals in the superficial dorsal horn of the spinal cord. This assertion is based on analysis of over 16,000 neurons from dorsal root ganglia in six rats.

See: Targeted Toxins

Zhang JJ, Song CG, Dai JM, Li L, Yang XM, Chen ZN (2022) Mechanism of opioid addiction and its intervention therapy: Focusing on the reward circuitry and mu-opioid receptor. MedComm 3(3):e148. doi: 10.1002/mco2.148 PMID: 35774845

Objective: To examine the mechanism of opioid addiction, with a specific focus on the reward circuitry and the role of the mu-opioid receptor, and to explore potential intervention therapies.

Summary: The authors discuss the neurobiological processes underlying addiction and highlight the importance of understanding these mechanisms in developing effective intervention therapies for opioid addiction.

Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12)

See Also:

• Jenrette TA et al. Lesions of the patch compartment of dorsolateral striatum disrupt stimulus-response learning. Neuroscience 415:161-172, 2019.

Ahn JP (2022) Ablation of dorsomedial striatum patch compartment results in modification to reward-driven behaviors in rats. Mercer University School of Medicine Thesis.

Objective: This thesis intended to demonstrate that selective ablation of dorsomedial striatum (DMS) patch compartment neurons results in a significant impact on the initial development of reward-driven behaviors during the early stages of drug seeking behavior.

Summary: Through the use Dermorphin-SAP and training rats to self-administer cocaine, ablation of the patch compartment of the DMS resulted in an increase in early-stage lever pressing, suggesting that the DMS patch compartment contributes to reward-driven behaviors.

Usage: 17 ng/µl Dermorphin-SAP in sterile artificial cerebrospinal fluid (aCSF) to selectively ablate patch compartment neurons. Infusions into either the dorsomedial striatum or dorsolateral striatum (2 µl of infusion liquid).

Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12)

Ahn J, Christy DJ, Horner K (2021) The role of the patch compartment of striatum in reward-driven behaviors. Neuroscience 2021 Abstracts P747/06. Society for Neuroscience, Virtual.

Summary: The striatum is a neural structure that plays a critical role in cognitive functions, behavioral decision-making, and reward generation. The striatum exhibits a heterogeneous composition, containing neurons belonging to the patch compartment—which is thought to be involved in habitual reward-related behaviors—surrounded by neurons belonging to the matrix compartment—which is thought to be involved in adaptive motor control. Additionally, the striatum is further subdivided into the dorsolateral striatum (DLS) and the dorsomedial striatum (DMS), each with their own patch and matrix compartments. The DMS has been associated with goal-oriented behavior seen during the initial stages of addiction. Conversely, the DLS has been associated with habitual behaviors seen during late-stage addictive behaviors that are inflexible. It is thought that drug addiction is initially mediated by the DMS before DLS activity becomes predominant. Previously, it has been shown that the patch compartment of the DLS is necessary for development of habitual behavior, but the role of the patch compartment of the DMS is less clear. Our study intends to demonstrate that selective ablation of DMS patch compartment neurons will result in a negative impact on the initial development of reward-driven behaviors during the early stages of drug addiction. Since patch compartment neurons express a high level of mu opioid receptors compared to the surrounding matrix, we used dermorphin-saporin, a toxin that selectively destroys mu opioid receptor-containing neurons to target patch compartment neurons in the DMS and DLS for ablation. Following infusion in the DMS or DLS with dermorphin-saporin (17 ng/μl) or vehicle, rats were trained to self-administer cocaine (0.4 mg/kg/infusion) on progressive ratio schedule of reinforcement, starting with fixed ratio of 1 and ending with a fixed ratio of 5. Ablation of the patch compartment altered the level of responding for cocaine as the schedule of reinforcement became progressively labor-intensive. These data suggest that the patch compartment contributes to reward-driven behaviors.

Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12)

Jenrette TA, Logue JB, Horner KA (2019) Lesions of the patch compartment of dorsolateral striatum disrupt stimulus-response learning. Neuroscience 415:161-172. doi: 10.1016/j.neuroscience.2019.07.033

Objective: To investigate whether enhanced activation of the patch compartment contributes to habitual behavior.

Summary: The dorsolateral patch compartment may mediate habit formation by altering information flow through basal ganglia circuits.

Usage: A volume of 2 ul of Dermorphin-SAP (17 ng/ul or an equivalent amount of unconjugated SAP (as a control) was infused bilaterally, at a rate of 0.5 ul/min.

Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12), Saporin (Cat. #PR-01)

Eidson LN, Murphy AZ (2019) Inflammatory mediators of opioid tolerance: Implications for dependency and addiction. Peptides 115:51-58. doi: 10.1016/j.peptides.2019.01.003

Objective: To determine what mediates opioid tolerance and alterations in glutamate homeostasis.

Summary: Site-specific lesions of PAG MOR-containing neurons using Dermorphin-SAP significantly reduce the antinociceptive effects of systemic morphine suggesting that PAG MOR is critical for morphine action.

Usage: Rats were injected with 3 pmol of Dermorphin-SAP (Cat. #IT-12) into the PAG. Blank-SAP (Cat. #IT-21) was used as a control.

See: Loyd DR et al. Sex differences in micro-opioid receptor expression in the rat midbrain periaqueductal gray are essential for eliciting sex differences in morphine analgesia. J Neurosci 28:14007-14017, 2008.

Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12), Blank-SAP (Cat. #IT-21)

Shumilov K, Real MÁ, Valderrama-Carvajal A, Rivera A (2018) Selective ablation of striatal striosomes produces the deregulation of dopamine nigrostriatal pathway. PLoS One 13:e0203135. doi: 10.1371/journal.pone.0203135

Objective: To increase knowledge in the role of the striosomal projection onto the dopamine neurons of the SNc and its impact on the nigrostriatal dopamine pathway.

Summary: Results highlight the key function of the striosomes for maintenance of the striatal dopamine tone and contribute to the understanding of their involvement in some neurological disorders such as Huntington’s disease.

Usage: Unilateral intrastriatal 2-μl injections of Dermorphin-SAP (17 μg/μl in saline) were performed to induce the selective ablation of MOR-expressing neurons in the striosomal compartment.

Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12)

Horner KA, Logue JB, Jenrette TA (2017) Patch compartment lesions reduce habitual sucrose consumption. Neuroscience 2017 Abstracts 689.16 / II23. Society for Neuroscience, Washington, DC.

Summary: The striatum mediates habit formation and reward association. The striatum can be divided into the patch and matrix compartment, which are two neurochemically and anatomically distinct regions that may sub-serve different aspects of behavior. For example, the patch compartment may mediate reward-related behaviors, while the matrix compartment may mediate adaptive motor functions. Furthermore, previous studies have shown that enhanced relative activation of the patch versus matrix compartment is associated with inflexible behaviors, such as stereotypy. Habitual behaviors are also inflexible in nature, but whether enhanced activation of the patch compartment contributes to habitual behavior is not known. The goal of the current study was to examine the role of patch compartment neurons in the development of habit formation. We used dermorphin-saporin to specifically ablate neurons of the patch compartment prior to training animals to self-administer sucrose on a random interval schedule of reinforcement, which has been shown to foster habit formation. Our data showed that destruction of the neurons of the patch compartment prevented the reinstatement of sucrose self-administration after sucrose devaluation, indicating that absence of the patch compartment interrupted the development of habitual behavior. Our data also indicate that c-Fos levels were decreased in the dorsolateral striatum (DLS) and sensorimotor cortex (SMC), but increased in dorsomedial striatum (DMS) and prefrontal cortex (PFC) in patch-lesioned animals that did not develop habitual behavior, indicating that diminished habit formation is associated with decreased activation of regions that participate in habitual behavior, and increased in regions associated with goal-directed behaviors. Together, these data indicate that the patch compartment participates in habit formation by altering the flow of information through basal ganglia circuits.

Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12)

Jenrette T, Logue J, Horner KA (2017) Striatal patch compartment lesions reduce habitual behaviors. FASEB J 31(S1):1059.6. Experimental Biology 2017 Meeting Abstracts. doi: 10.1096/fasebj.31.1_supplement.1059.6

Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12)