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Fulltext Divergent Solutions to Visual Problem Solving across Mammalian Species

Mustafar F, Harvey MA, Khani A, Arató J, Rainer G

eNeuro, 2018 07 11;5(4).
PMID: 30073190 DOI: 10.1523/ENEURO.0167-18.2018

Our understanding of the neurobiological underpinnings of learning and behavior relies on the use of invasive techniques, which necessitate the use of animal models. However, when different species learn the same task, to what degree are they actually producing the same behavior and engaging homologous neural circuitry? This question has received virtually no recent attention, even as the most powerful new methodologies for measuring and perturbing the nervous system have become increasingly dependent on the use of murine species. Here, we test humans, rats, monkeys, and an evolutionarily intermediate species, tree shrews, on a three alternative, forced choice, visual contrast discrimination task. As anticipated, learning rate, peak performance, and transfer across contrasts was lower in the rat compared to the other species. More interestingly, rats exhibited two major behavioral peculiarities: while monkeys and tree shrews based their choices largely on visual information, rats tended to base their choices on past reward history. Furthermore, as the task became more difficult, rats largely disengaged from the visual stimulus, reverting to innate spatial predispositions in order to collect rewards near chance probability. Our findings highlight the limitation of muridae as models for translational research, at least in the area of visually based decision making.

Matched MeSH terms: Conditioning, Operant/physiology*
Discriminative stimulus properties of mitragynine (kratom) in rats

Harun N, Hassan Z, Navaratnam V, Mansor SM, Shoaib M

Psychopharmacology (Berl), 2015 Jul;232(13):2227-38.
PMID: 25616583 DOI: 10.1007/s00213-015-3866-5

RATIONALE: Mitragynine (MG) is the primary active alkaloid extracted from the leaves of Mitragyna speciosa or kratom and exhibits pharmacological activities mediated by opioid receptors. The plant has been traditionally used for its opium and psychostimulant-like effects to increase work efficiency or as a substitute in the self-treatment of opiate addiction.
OBJECTIVES: The present study was performed to investigate the discriminative stimulus effects of MG in rats. The pharmacological mechanism of MG action and its derivative, 7-hydroxymitragynine (7-HMG) with a specific focus on opioid receptor involvement was examined in rats trained to discriminate morphine from vehicle. In order to study the dual actions of MG, the effect of cocaine substitution to the MG discriminative stimulus was also performed in MG-trained rats.
METHODS: Male Sprague Dawley rats were trained to discriminate MG from vehicle in a two-lever drug discrimination procedure under a tandem variable-interval (VI 60') fixed-ratio (FR 10) schedule of food reinforcement.
RESULTS: Rats acquired the MG discrimination (15.0 mg/kg, i.p.) which was similar to the acquisition of morphine discrimination (5.0 mg/kg, i.p.) in another group of rats. MG substituted fully to the morphine discriminative stimulus in a dose-dependent manner, suggesting pharmacological similarities between the two drugs. The administration of 7-HMG derivative in 3.0 mg/kg (i.p.) dose engendered full generalisation to the morphine discriminative stimulus. In addition, the MG stimulus also partially generalised to cocaine (10.0 mg/kg, i.p.) stimulus.
CONCLUSION: The present study demonstrates that the discriminative stimulus effect of MG possesses both opioid- and psychostimulant-like subjective effects.

Matched MeSH terms: Conditioning, Operant/physiology
Assessing physiological dependence and withdrawal potential of mitragynine using schedule-controlled behaviour in rats

Harun N, Johari IS, Mansor SM, Shoaib M

Psychopharmacology (Berl), 2020 Mar;237(3):855-867.
PMID: 31832720 DOI: 10.1007/s00213-019-05418-6

RATIONALE: Kratom is proposed to exhibit therapeutic potential as an opium substitute, but little is known about its dependence-producing profile, particularly of its main psychoactive compound, mitragynine (MG).
OBJECTIVES: This study examined the dependence-producing effects of MG using operant-scheduled behaviour in rats and investigated the potential therapeutic effect of MG by comparing effects to buprenorphine in morphine-dependent rats using the same schedule-controlled behavioural task.
METHODS: The effects of acutely administered MG and morphine were determined in rats trained to respond under fixed-ratio (FR) 10 schedule of food reinforcement. Next, the rats were administered MG and morphine twice daily for 14 consecutive days to determine if physiological dependence would develop by examining cessation of drug treatment and following antagonist-precipitated withdrawal. The study then examined the effects of MG substitution to suppress naloxone-precipitated morphine withdrawal effects on scheduled responding.
RESULTS: Acute doses of MG did not produce dose-related decreases on FR schedules of responding compared to morphine. Unlike morphine, MG-treated rats showed no suppression of response rates following cessation of MG treatment. However, withdrawal effects were evident for MG after precipitation by either naloxone or SR141716A (rimonabant), similar to morphine-treated rats. MG in higher doses (10 and 30 mg/kg) attenuated the naloxone-precipitated morphine withdrawal effects while smaller doses of buprenorphine (0.3 and 1.0 mg/kg) were necessary to alleviate these effects.
CONCLUSION: The findings suggest that MG does not induce physiological dependence but can alleviate the physical symptoms associated with morphine withdrawal which represent the desired characteristics of novel pharmacotherapeutic interventions for managing opioid use disorder (OUD).

Matched MeSH terms: Conditioning, Operant/physiology

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