Serotonin 2C receptor (5-HT2CR) agonists administered systemically attenuate both cocaine-primed and cue-elicited reinstatement of extinguished cocaine-seeking behavior. To further elucidate the role of these receptors in addiction-like processes, this study examined the effects of microinfusing the 5-HT2CR agonist MK212 (0, 10, 30, 100 ng/side/0.2µl) into the medial prefrontal cortex (mPFC) on cocaine self-administration and reinstatement of extinguished cocaine-seeking behavior. Male Sprague-Dawley rats were trained to self-administer cocaine (0.75 mg/kg, i.v.) paired with light and tone cues. Once responding stabilized, rats received MK212 microinfusions prior to tests for maintenance of cocaine self-administration. Next, extinction training to reduce cocaine-seeking behavior, defined as responses performed without cocaine reinforcement available, occurred until low extinction baselines were achieved. Rats then received MK212 microinfusions prior to tests for reinstatement of extinguished cocaine-seeking behavior elicited by cocaine-priming injections (10 mg/kg, i.p.) or response-contingent presentations of the cocaine-associated cues; operant responses during cocaine-primed reinstatement tests produced no consequences. MK212 microinfusions into the prelimbic and infralimbic, but not anterior cingulate, regions of the mPFC dose-dependently attenuated both cocaine-primed and cue-elicited reinstatement of extinguished cocaineseeking behavior but did not reliably affect cocaine self-administration. A subsequent experiment demonstrated that the effects of MK212 (100 ng/side/0.2µl) on reinstatement of extinguished cocaine-seeking behavior were blocked by co-administration of the 5-HT2CR antagonist SB242084 (200 ng/side/0.2µl). MK212 administered alone into the mPFC as a drug prime produced no discernable effects on cocaine-seeking behavior. These findings suggest that stimulation of 5-HT2CRs in the mPFC attenuates the incentive motivational effects produced by sampling cocaine or exposure to drug-paired cues.

A formalin-fixed left, blue eye, from a 9-year-old, spayed female beagle dog was submitted to the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) for light microscopic evaluation. The history included glaucoma and an abnormal appearance for 6 months and then the development of a uveal mass. The histologic diagnosis was a spindle cell tumor of blue-eyed dogs (SCTBED). In June of 2012, the dog was euthanized due to ailing health, and there was radiographic and postmortem examination evidence of neoplastic metastasis. This is the first reported case of this primary ocular neoplasm metastasizing, and we propose to rename SCTBED as a uveal schwannoma of blue-eyed dogs.

Iridociliary tumors are the second most common primary ocular tumor in dogs and are usually benign. A review of the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) database in 2009 suggested a potential correlation between malignant iridociliary epithelial tumors and ciliary body ablation by intravitreal gentamicin injection for the treatment of glaucoma. The purpose of this case series was to determine whether there is evidence of such a correlation in the COPLOW collection. Mining of the COPLOW database revealed that a significant number (39.5%) of canine globes with a history of ciliary body ablation were subsequently diagnosed with primary ocular tumors at enucleation, most commonly iridociliary epithelial tumors and melanocytic tumors. It is possible that neoplasia was present but unrecognized at the time of ciliary body ablation. These tumors had a higher than expected incidence of malignancy. These cases underscore the importance of reserving ciliary body ablation with gentamicin for disease-free eyes.

Practitioners approach chemical ciliary body ablation (CBA) in cats with caution. In 1994, an academic letter proposed a potential link between intraocular gentamicin injections for glaucoma and the appearance of ocular tumors in cats (Veterinary and Comparative Ophthalmology, 4, 1994, 166). There is an historic perceived risk for the development of feline ocular post-traumatic sarcoma following gentamicin ciliary body ablation, and many clinicians refrain from chemical ablation in cats for this reason. A recent study discussed the possibility of a correlation between intravitreal gentamicin and tumor promotion in dogs (Veterinary Ophthalmology, 16, 2013, 159). We searched the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) database for cases of cats diagnosed with ocular tumors following ciliary body ablation. Of eight cases with historic gentamicin injection, five had malignant tumors: three post-traumatic sarcomas and two melanomas.

The formalin-fixed, amber-colored right globe from a 12-week-old female silver Labrador Retriever dog was submitted to the Comparative Ocular Pathology Laboratory of Wisconsin for light microscopic evaluation. The clinical history described a collapsed anterior chamber and multifocal nodular lesions in the peripheral iris. Histologically, immunohistochemically, and ultrastructurally, the uveal mass was consistent with a malignant schwannoma; there was extension along peripheral nerves within the sclera. The signalment and behavior of the neoplasm distinguish it from the uveal schwannoma of blue-eyed dogs and bear some resemblance to the ocular lesions in human neurofibromatosis. The dilute color mutation may contribute to the cause. Six weeks later, the dog did not develop any additional masses.