Abstract
Rationale
The affective aspects of d-amphetamine (AMPH) may be mediated, in part, by cocaine- and amphetamine-regulated transcript (CART) peptides in the basolateral amygdala (BLA). The formation of context-drug associations produces either conditioned place preference (CPP) or conditioned place aversion (CPA).
Objectives
The aim of the present study was to determine whether intra-BLA infusions of CART 55–102 are either rewarding or aversive and modulate AMPH reward.
Materials and methods
Rats were implanted with bilateral cannulae in the BLA, were subjected to place conditioning, and were tested for CPP or CPA. Rats were conditioned with either intra-BLA infusions of artificial cerebral spinal fluid or one of three dose of CART 55–102 (1, 2, or 4 μg/side), intra-BLA infusions of a subrewarding dose of CART 55–102 (1 μg/side) plus injections of a subrewarding dose of AMPH (0.1 mg/kg, i.p.), or intra-BLA infusions of an aversive dose of CART 55–102 (4 μg/side) plus injections of a rewarding dose of AMPH (1.0 mg/kg, i.p.).
Results
Intra-BLA infusions of 2 μg/side CART 55–102 produced CPP, 4 μg/side produced CPA, and 1 μg/side produced neither CPP nor CPA. Intra-BLA infusions of a subrewarding dose of CART 55–102 (1 μg/side) plus injections of a subrewarding dose of AMPH (0.1 mg/kg, i.p.) produced CPP. Intra-BLA infusions of an aversive dose of CART 55–102 (4 μg/side) plus injections of a rewarding dose of AMPH (1.0 mg/kg, i.p.) produced neither CPP nor CPA.
Conclusions
Both the affective properties of intra-BLA CART 55–102 and its ability to either facilitate or block AMPH reward are dose dependent.
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References
Asan E (1997) Ultrastructural features of tyrosine-hydroxylase-immunoreactive afferents and their targets in the rat amygdala. Cell Tissue Res 288:449–469
Asan E (1998) The catecholaminergic innervation of the rat amygdala. Adv Anat Embryol Cell Biol 142:1–118
Bardo MT, Bevins RA (2000) Conditioned place preference: what does it add to our preclinical understanding of drug reward? Psychopharmacology (Berl) 153:31–43
Brady AM, O’Donnell P (2004) Dopaminergic modulation of prefrontal cortical input to nucleus accumbens neurons in vivo. J Neurosci 24:1040–1049
Cahill L, McGaugh JL (1998) Mechanisms of emotional arousal and lasting declarative memory. Trends Neurosci 21:294–299
Canteras NS, Swanson LW (1992) Projections of the ventral subiculum to the amygdala, septum, and hypothalamus: a PHAL anterograde tract-tracing study in the rat. J Comp Neurol 324:180–194
Cardinal RN, Parkinson JA, Hall J, Everitt BJ (2002) Emotion and motivation: the role of the amygdala, ventral striatum, and prefrontal cortex. Neurosci Biobehav Rev 26:321–352
Carlezon WA Jr, Chartoff EH (2007) Intracranial self-stimulation (ICSS) in rodents to study the neurobiology of motivation. Nat Protoc 2:2987–2995
Carlezon WA Jr, Thomas MJ (2009) Biological substrates of reward and aversion: a nucleus accumbens activity hypothesis. Neuropharmacology 56(Suppl 1):122–132
Cechetto DF, Saper CB (1987) Evidence for a viscerotopic sensory representation in the cortex and thalamus in the rat. J Comp Neurol 262:27–45
Chaki S, Kawashima N, Suzuki Y, Shimazaki T, Okuyama S (2003) Cocaine- and amphetamine-regulated transcript peptide produces anxiety-like behavior in rodents. Eur J Pharmacol 464:49–54
Cota D, Marsicano G, Tschöp M, Grübler Y, Flachskamm C, Schubert M, Auer D, Yassouridis A, Thöne-Reineke C, Ortmann S, Tomassoni F, Cervino C, Nisoli E, Linthorst AC, Pasquali R, Lutz B, Stalla GK, Pagotto U (2003) The endogenous cannabinoid system affects energy balance via central orexigenic drive and peripheral lipogenesis. J Clin Invest 112:423–431
Couceyro PR, Evans C, McKinzie A, Mitchell D, Dube M, Hagshenas L, White FJ, Douglass J, Richards WG, Bannon AW (2005) Cocaine- and amphetamine-regulated transcript (CART) peptides modulate the locomotor and motivational properties of psychostimulants. J Pharmacol Exp Ther 315:1091–1100
Dallvechia-Adams S, Kuhar MJ, Smith Y (2002) Cocaine- and amphetamine-regulated transcript peptide projections in the ventral midbrain: colocalization with gamma-aminobutyric acid, melanin-concentrating hormone, dynorphin, and synaptic interactions with dopamine neurons. J Comp Neurol 448:360–372
Everitt BJ, Morris KA, O’Brien A, Robbins TW (1991) The basolateral amygdala-ventral striatal system and conditioned place preference: further evidence of limbic-striatal interactions underlying reward-related processes. Neuroscience 42:1–18
Fabri M, Burton H (1991) Ipsilateral cortical connections of primary somatic sensory cortex in rats. J Comp Neurol 311:405–424
Fagergren P, Hurd YL (1999) Mesolimbic gender differences in peptide CART mRNA expression: effects of cocaine. Neuroreport 10:3449–3452
Fuchs RA, Weber SM, Rice HJ, Neisewander JL (2002) Effects of excitotoxic lesions of the basolateral amygdala on cocaine-seeking behavior and cocaine conditioned place preference. Brain Res 929:15–25
Haller J, Varga B, Ledent C, Barna I, Freund TF (2002) The effects of genetic and pharmacological blockade of the CB1 cannabinoid receptor on anxiety. Eur J Neurosci 19:1395–1398
Helmstetter FJ, Bellgowan PS (1994) Effects of muscimol applied to the basolateral amygdala on acquisition and expression of contextual fear conditioning in rats. Behav Neurosci 108:1005–1009
Hiroi N, White NM (1991) The lateral nucleus of the amygdala mediates the expression of the amphetamine-produced conditioned place preference. J Neurosci 11:2107–2116
Hsu EH, Schroeder JP, Packard MP (2002) The amygdala mediates memory consolidation for an amphetamine conditioned place preference. Behav Brain Res 129:93–100
Jaworski JN, Jones DC (2006) The role of CART in the rewarding/reinforcing properties of psychostimulants. Peptides 27:1993–2004
Jaworski JN, Kozel MA, Philpot KB, Kuhar MJ (2003) Intra-accumbal injection of CART (cocaine-amphetamine regulated transcript) peptide reduces cocaine-induced locomotor activity. J Pharmacol Exp Ther 307:1038–1044
Jones DC, Kuhar MJ (2008) CART receptor binding in primary cell cultures of the rat nucleus accumbens. Synapse 62:122–127
Kathuria S, Gaetani S, Fegley D, Valiño F, Duranti A, Tontini A, Mor M, Tarzia G, La Rana G, Calignano A, Giustino A, Tattoli M, Palmery M, Cuomo V, Piomelli D (2003) Modulation of anxiety through blockade of anandamide hydrolysis. Nat Med 9:76–81
Katona I, Rancz EA, Acsady L, Ledent C, Mackie K, Hajos N, Freund TF (2001) Distribution of CB1 cannabinoid receptors in the amygdala and their role in the control of GABAergic transmission. J Neurosci 21:9506–9518
Kimmel HL, Gong W, Vechia SD, Hunter RG, Kuhar MJ (2000) Intra-ventral tegmental area injection of rat cocaine and amphetamine-regulated transcript peptide 55–102 induces locomotor activity and promotes conditioned place preference. J Pharmacol Exp Ther 294(2):784–792
Koob GF, Swerdlow NR (1988) The functional output of the mesolimbic dopamine system. Ann N Y Acad Sci 537:216–227
Koylu EO, Couceyro PR, Lambert PD, Kuhar MJ (1998) Cocaine- and amphetamine-regulated transcript peptide immunohistochemical localization in the rat brain. J Comp Neurol 391:115–132
Lakatos A, Prinster S, Vicentic A, Hall RA, Kuhar MJ (2005) Cocaine- and amphetamine-regulated transcript (CART) peptide activates the extracellular signal-regulated kinase (ERK) pathway in AtT20 cells via putative G-protein coupled receptors. Neurosci Lett 384:198–202
LeDoux JE (1993) Emotional memory: in search of systems and synapses. Ann N Y Acad Sci 702:149–157
LeDoux JE (2000) Emotion circuits in the brain. Ann Rev Neurosci 23:155–184
LeDoux JE, Ruggiero DA, Reis DJ (1985) Projections to the subcortical forebrain from anatomically defined regions of the medial geniculate body in the rat. J Comp Neurol 242:182–213
LeDoux JE, Farb C, Ruggiero DA (1990) Topographic organization of neurons in the acoustic thalamus that project to the amygdala. J Neurosci 10:1043–1054
LeDoux JE, Farb CR, Romanski LM (1991) Overlapping projections to the amygdala and striatum from auditory processing areas of the thalamus and cortex. Neurosci Lett 134:139–144
Mascagni F, McDonald AJ, Coleman JR (1993) Corticoamygdaloid and corticocortical projections of the rat temporal cortex: a Phaseolus vulgaris leucoagglutinin study. Neuroscience 57:697–715
McDonald AJ, Jackson TR (1987) Amygdaloid connections with posterior insular and temporal cortical areas in the rat. J Comp Neurol 262:59–77
Mogenson GJ, Jones DL, Yim CY (1980) From motivation to action: functional interface between the limbic system and the motor system. Prog Neurobiol 14:69–97
Mucha RF, van der Kooy D, O’Shaughnessy M, Bucenieks P (1982) Drug reinforcement studied by the use of place conditioning in rat. Brain Res 243:91–105
Muller J, Corodimas KP, Fridel Z, LeDoux JE (1997) Functional inactivation of the lateral and basal nuclei of the amygdala by muscimol infusion prevents fear conditioning to an explicit conditioned stimulus and to contextual stimuli. Behav Neurosci 111:683–691
Muller JF, Mascagni F, McDonald AJ (2009) Dopaminergic innervation of pyramidal cells in the rat basolateral amygdala. Brain Struct Funct 213:275–288
Osei-Hyiaman D, Depetrillo M, Harvey-White J, Bannon AW, Cravatt BF, Kuhar MJ, Mackie K, Palkovits M, Kunos G (2005) Cocaine- and amphetamine-related transcript is involved in the orexigenic effect of endogenous anandamide. Neuroendocrinology 81:273–282
Ottersen OP (1982) Connections of the amygdala of the rat. IV: corticoamygdaloid and intraamygdaloid connections as studied with axonal transport of horseradish peroxidase. J Comp Neurol 205:30–48
Paré D, Smith Y, Paré JF (1995) Intra-amygdaloid projections of the basolateral and basomedial nuclei in the cat: Phaseolus vulgaris-leucoagglutinin anterograde tracing at the light and electron microscopic level. Neuroscience 69:567–583
Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates, 6th edn. Academic, New York
Rademacher DJ, Kovacs B, Shen F, Napier TC, Meredith ME (2006) The neural substrates of amphetamine conditioned place preference: implications for the formation of conditioned stimulus–reward associations. Eur J Neurosci 24:2089–2097
Rademacher DJ, Meier SE, Shi L, Ho WS, Jarrahian A, Hillard CJ (2008) Effects of acute and repeated restraint stress on endocannabinoid content in the amygdala, ventral striatum, and medial prefrontal cortex in mice. Neuropharmacology 54:108–116
Rogge G, Jones D, Hubert GW, Lin Y, Kuhar MJ (2008) CART peptides: regulators of body weight, reward and other functions. Nat Rev Neurosci 9:747–758
Rosenkranz JA, Moore H, Grace AA (2003) The prefrontal cortex regulates lateral amygdala neuronal plasticity and responses to previously conditioned stimuli. J Neurosci 23:11054–11064
Rossi NA, Reid LD (1976) Affective states associated with morphine injections. Physiol Psychol 4:535–538
Sah P, Faber ES, Lopez De Armentia M, Power J (2003) The amygdaloid complex: anatomy and physiology. Physiol Rev 83:803–834
Sarkar S, Wittman G, Fekete C, Lechan RM (2004) Central administration of cocaine- and amphetamine-regulated transcript increases phosphorylation of cAMP response element binding protein in corticotrophin-releasing hormone-producing neurons but not in prothyrotropin-releasing hormone-producing neurons in the hypothalamic paraventricular nucleus. Brain Res 999:181–192
Schroeder JP, Packard MG (2002) Posttraining intra-basolateral amygdala scopolamine impairs food- and amphetamine-induced conditioned place preferences. Behav Neurosci 116:922–927
Segal DS, Mandell AJ (1974) Long-term administration of d-amphetamine: progressive augmentation of motor activity and stereotypy. Pharmacol Biochem Behav 2:249–255
Shen F, Meredith GE, Napier TC (2006) Amphetamine-induced place preference and conditioned motor sensitization requires activation of tyrosine kinase receptors in the hippocampus. J Neurosci 26:11041–11051
Smith Y, Koylu EO, Couceyro P, Kuhar MJ (1997) Ultrastructural localization of CART (cocaine- and amphetamine-regulated transcript) peptides in the nucleus accumbens of monkeys. Synapse 27:90–94
Spyraki C, Fibiger HC, Phillips AG (1982) Dopaminergic substrates of amphetamine-induced place preference conditioning. Brain Res 253:185–193
Turner BH, Herkenham M (1991) Thalamoamygdaloid projections in the rat: a test of the amygdala’s role in sensory processing. J Comp Neurol 313:295–325
Tzschentke TM (1998) Measuring reward with the conditioned place preference paradigm: a comprehensive review of drug effects, recent progress and new issues. Prog Neurobiol 56:613–672
Vicentic A, Jones DC (2007) The CART (cocaine- and amphetamine-regulated transcript) system in appetite and drug addiction. J Pharmacol Exp Ther 320:499–506
Yermolaieva O, Chen J, Couceyro PR, Hoshi T (2001) Cocaine- and amphetamine-regulated transcript peptide modulation of voltage-gated Ca2+ signaling in hippocampal neurons. J Neurosci 21:7474–7480
Acknowledgments
The authors thank Philip Dougherty and IhteshamUr Rahman for technical assistance. This research was supported by National Institute on Drug Abuse grant DA015513.
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The authors have no actual or potential conflict of interest in relation to this article.
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Rademacher, D.J., Sullivan, E.M. & Figge, D.A. The effects of infusions of CART 55–102 into the basolateral amygdala on amphetamine-induced conditioned place preference in rats. Psychopharmacology 208, 499–509 (2010). https://doi.org/10.1007/s00213-009-1748-4
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DOI: https://doi.org/10.1007/s00213-009-1748-4