Department of Psychology

Pharmacology and Neuroanatomy of Conditioned Flavor Preferences

Animals use flavor cues (taste, odor, texture) to guide their selection of nutritious foods and avoidance of toxic foods. One type of learning, called flavor-flavor conditioning, occurs when a preference is acquired for an arbitrary flavor cue (e.g., banana) paired with an already liked flavor (e.g., sweet taste of saccharin). The sweet taste is considered to be an unconditioned stimulus (US) that reinforces the animal’s preference for the added flavor, which represents the conditioned stimulus (CS). In a decade-long collaboration with the laboratory of Dr. Anthony Sclafani (Brooklyn College, CUNY), we evaluated the pharmacology and neuroanatomy of these conditioned flavor preferences with our laboratory examining oral consequences (flavor-flavor conditioning) and the Sclafani laboratory examining post-ingestive consequences (flavor-nutrient conditioning). Flavor-flavor conditioning can be investigated in two ways: a) comparing preferences for a sucrose-paired flavor (the CS+) relative to a saccharin-paired flavor (the CS-) using a sham-feeding procedure in which rats fitted with a gastric cannula to reduce the post-oral actions of sucrose; and b) comparing preferences for a combined fructose/saccharin-paired flavor (the CS+) relative to a saccharin-paired flavor (the CS-) using real-feeding rats because fructose has minimal post-oral flavor conditioning effects.

In initial systemic studies, our laboratories found a role for dopamine, and particularly D1 receptors mediating the acquisition and expression of flavor-flavor conditioning using sucrose and fructose, and a role for D1 receptors in the acquisition of flavor-nutrient conditioning. In contrast, although systemic opioid receptor antagonism with naltrexone reduced sweet intake per se, it failed to alter the acquisition or expression of either flavor-flavor or flavor-nutrient conditioning. Systemic antagonism of cannabinoid CB1 receptors produced moderate reductions in the expression of flavor-flavor conditioning. Our laboratories received NIH (NIDDK) funding to explore the neuroanatomical substrates of flavor-flavor and flavor-nutrient conditioning by performing antagonist studies in the nucleus accumbens, amygdala, lateral hypothalamus and medial prefrontal cortex. Parallel studies also examined the underlying pharmacology mediating fat-conditioned flavor preferences by pairing one novel flavor with a higher Intralipid concentration and a second novel flavor with a lower Intralipid concentration.

Conditioned Flavor Preference Publications of the Bodnar Laboratory:

Bodnar, RJ Conditioned flavor preferences in animals: merging pharmacology, brain sites and genetic variance. A Festschrift to Drs. Anthony Sclafani and Karen Ackroff. Appetite 122: 17-25, 2018.

Rotella, FM, K Olsson, N Martinez, A Mordo, I Kohen,  A Aminov, J Pagirsky, A Yu, V Vig and RJ Bodnar. Muscarinic, nicotinic and GABAergic receptor signaling differentially mediates fat-conditioned flavor preferences in rats. Pharmacol Biochem Behav 150-151: 14-21, 2016.

Rotella, FM, V Vig, K Olsson, J Pagirsky, A Aminov, I Kohen, and RJ Bodnar. Baclofen differentially mediates fructose-conditioned flavor preference and quinine-conditioned flavor avoidance in rats. Eur J Pharm 775: 15-21, 2016.

Dela Cruz J, T Coke and RJ Bodnar. Simultaneous detection of c-fos activation from mesolimbic and mesocortical dopamine reward sites following naïve sugar and fat ingestion in rats. Journal of Visualized Experiments (JoVE) 114: e53897, 2016.

Rotella, FM, K Olsson, V Vig, I Yenko, J Pagirsky, I Kohen, A Aminov, T Dindyal and RJ Bodnar. Muscarinic and nicotinic cholinergic receptor antagonists differentially mediate acquisition of fructose-conditioned flavor preference and quinine-conditioned flavor avoidance in rats. Neurobiol Learn Mem 123: 239-249, 2015.

Dela Cruz J, T Coke, T Karagiorgis, C Sampson, D Icaza-Cukali, K Kest, R Ranaldi and RJ Bodnar. C-fos induction in mesotelencephalic dopamine pathway projection targets and dorsal striatum following oral intake of sugars and fats in rats. Brain Res Bull 111: 9-19, 2015.

Malkusz DC, I Yenko, FM Rotella, T Banakos, T Dindyal, K Olsson, V Vig and RJ Bodnar. Dopamine signaling in the medial orbital frontal cortex and the acquisition and expression of fructose-conditioned flavor preferences in rats. Brain Res 1596: 116-125, 2015.

Dela Cruz J, T Coke, D Icaza-Cukali, N Kalifa and RJ Bodnar. Roles of NMDA and dopamine D1 and D2 receptors in the acquisition and expression of flavor preferences conditioned by oral glucose in rats. Neurobiol Learn Mem 114: 223-230, 2014.

Malkusz, DC, SY Bernal, T Banakos, G Malkusz, A Mohamed, T Vongwattanakit and RJ Bodnar. Evaluation of saccharin intake and expression of fructose-conditioned flavor preferences following opioid receptor antagonism in the medial prefrontal cortex, amygdala or lateral hypothalamus in rats. Neurosci Lett 564: 94-98, 2014.

Rotella, FM, A Badalia, SM Duenas, M Hossain, S Saeed, K Touzani, A Sclafani and RJ Bodnar. Role of NMDA, opioid and dopamine D1 and D2 receptor signaling in the acquisition of a quinine-conditioned flavor avoidance in rats. Physiol Behav 128: 133-140, 2014.

Amador, N, FM Rotella, S Y Bernal, D Malkusz, J Dela Cruz, A Badalia, SM Duenas, M Hossain, M Gerges, S Kandov, K Touzani, A Sclafani and RJ Bodnar. Effect of dopamine D1 and D2 receptor antagonism in the lateral hypothalamus on the expression and acquisition of fructose-conditioned flavor preference in rats. Brain Res 1542: 70-78, 2014.

Touzani K, RJ Bodnar and A Sclafani. Glucose conditioned-flavor preference learning requires co-activation signaling at NMDA and dopamine D1-like receptors within the amygdala. Neurobiol. Learn Mem 106: 95-101, 2013.

Dela Cruz, J, VS Bae, DP Icaza-Cukali, C Sampson, D Bamshad, A Samra, S Singh, N Khalifa , K Touzani, A Sclafani and RJ Bodnar. Critical role of NMDA but not opioid receptors in the acquisition of fat-conditioned flavor preferences in rats. Neurobiol Learn Mem 98: 341-347, 2012.

Malkusz DC, T Banakos, A Mohamed, T Vongwattanakit, G Malkusz, S Saeed, S Martinez, T Bohn, F Mahmud, C Liss, A Rozvi, K Touzani, A Sclafani and RJ Bodnar. Dopamine signaling in the medial prefrontal cortex and amygdala is required for the acquisition of fructose-conditioned flavor preferences in rats. Behav Brain Res 233: 500-507, 2012.

Dela Cruz, J, DP Icaza-Cukali, H Tayabali, V Galanopoulos, C Sampson, D Bamshad, K Touzani, A Sclafani and RJ Bodnar. Roles of dopamine D1 and D2 receptors in the acquisition and expression of fat-conditioned flavor preferences in rats. Neurobiol Learn Mem 97: 332-337, 2012.

Sclafani A, K Touzani and RJ Bodnar. Dopamine and learned food preferences. Invited review from Bartley Hoebel Festschrift. Physiol Behav 104: 64-68, 2011.

Bonacchi K, K Ackroff, K Touzani, RJ Bodnar and A Sclafani. Opioid mediation of starch and sugar preference in the rat. Pharmacol Biochem Behav 96: 507-514, 2010.

Touzani K, RJ Bodnar and A Sclafani. Acquisition of glucose-conditioned flavor preference requires the activation of dopamine D1-like receptors within the medial prefrontal cortex in rats. Neurobiol Lng Mem 94: 214-219, 2010.

Touzani K, RJ Bodnar and A Sclafani. Pharmacology of food learning preferences. Pharmacol Biochem Behav 97: 55-62, 2010.

Bernal S, K Touzani, M Gerges, Y Abayev, A Sclafani and RJ Bodnar. Examination of naltrexone effects in the nucleus accumberns shell and core upon flavor-flavor preferences conditioned by fructose and flavor-nutrient preferences conditioned by intragastric glucose in rats. Pharmacol. Biochem. Behav. 95: 56-62, 2010.

Bernal S, K Touzani, M Gerges, Y Abayev, A Sclafani and RJ Bodnar. Examination of naltrexone effects in the nucleus accumberns shell and core upon flavor-flavor preferences conditioned by fructose and flavor-nutrient preferences conditioned by intragastric glucose in rats. Pharmacol. Biochem. Behav., in review, 2009.

Touzani, K, RJ Bodnar and A Sclafani. A role of the lateral hypothalamic dopamine D1 receptors in intragastric glucose-conditioned flavor preferences in rats. Neurobiol. Learning Mem. 92: 464-467, 2009.

Touzani, K, RJ Bodnar and A Sclafani. Dopamine D1-like receptor antagonism in amygdala impairs the acquisition of glucose-conditioned flavor preferences in rats. Eur J Neurosci.30: 289-298, 2009.

Bernal S, P Miner, Y Abayev, E Kandova, M Gerges, K Touzani, A Sclafani and RJ Bodnar. Role of amygdala dopamine D1 and D2 receptors in the acquisition and expression of fructose-conditioned flavor preferences in rats. Behav Brain Res. 205: 183-190, 2009.

Miner, P, Y Abayev, E Kandova, M Gerges, T Styler, R Wapniak, K Touzani, A Sclafani and RJ Bodnar. Role of systemic endocannabinoids CB-1 receptor antagonism in the acquisition and expression of fructose-conditioned flavor-flavor preferences in rats. Pharmacol Biochem Behav 90: 318-324, 2008.

Bernal S, I Dostova, A Kest, Y Abayev, E Kandova, K Touzani, A Sclafani and RJ Bodnar. Role of dopamine D1 and D2 receptors in the nucleus accumbens shell on the acquisition and expression of fructose-conditioned flavor-flavor preferences in rats. Behav Brain Res. 190: 59-66, 2008.

Touzani K, RJ Bodnar, and A Sclafani. Activation of dopamine D1 receptors in nucleus accumbens is critical for the acquisition, but not the expression, of glucose-conditioned flavor preference in rats. Eur J Neurosci 27: 1525-1533, 2008.

Baker, RW, Y Li, MG Lee, A Sclafani and RJ Bodnar. Naltrexone does not prevent acquisition or expression of flavor preferences conditioned by fructose in rats. Pharmacol. Biochem. Behav. 78: 239-246, 2004.

Baker, RM, MJ Shah, A Sclafani and RJ Bodnar. Dopamine D-1 and D-2 antagonists reduce the acquisition and expression of flavor preferences conditioned by fructose in rats. Pharmacol. Biochem. Behav. 75: 55-65, 2003.

Baker, RW, J Osman and RJ Bodnar. Differential actions of dopamine receptor antagonism in rats upon food intake elicited by either mercaptoacetate or exposure to a high-fat diet. Pharmacol. Biochem. Behav. 69: 201-208, 2001.

Azzara, AV, RJ Bodnar, AR Delamater and A Sclafani. D1 but not D2 dopamine receptor antagonism blocks the acquisition of a flavor preference conditioned by intragastric carbohydrate infusions. Pharmacol. Biochem. Behav. 68: 709-720, 2001.

Azzara, AV, RJ Bodnar , AR Delamater and A Sclafani. Naltrexone fails to block the acquisition or expression of a flavor preference conditioned by intragastric carbohydrate infusions. Pharmacol. Biochem. Behav. 67: 545-557, 2000.

Yu, W-Z, RM Silva, A Sclafani, AR Delamater and RJ Bodnar. Dopamine receptor subtype antagonists reduce the expression, but not the acquisition of flavor preference conditioning in sham-feeding rats. Pharmacol. Biochem. Behav. 67: 537-544, 2000.

Delamater, AR, A Sclafani and RJ Bodnar. Pharmacology of sucrose-reinforced place preference conditioning: effects of naltrexone. Pharmacol. Biochem. Behav. 65: 697-704, 2000.

Yu, W-Z, RM Silva, A Sclafani, AR Delamater and RJ Bodnar. Pharmacology of flavor preference conditioning in sham-feeding rats: effects of dopamine receptor antagonists. Pharmacol. Biochem. Behav. 65: 635-647, 2000.

Yu, W-Z, A Sclafani, AR Delamater and RJ Bodnar. Pharmacology of flavor preference conditioning in sham-feeding rats: effects of naltrexone. Pharmacol. Biochem. Behav. 64: 573-584, 1999.