Abstract
Rationale
Preclinical models of cocaine addiction in the rodent have shown that cocaine induces both positive and negative affective states. These observations have led to the notion that the initial positive/euphoric state induced by cocaine administration may be followed by an opposing, negative process. In the rodent, one method for inferring positive and negative affective states involves measuring their ultrasonic vocalizations (USVs). Previous USV recordings from our laboratory suggested that the transition between positive and negative affect might involve decaying or sub-satiety levels of self-administered cocaine.
Objectives
In order to explicitly test the role of cocaine levels on these affective states, the present study examined USVs when calculated body levels of cocaine were clamped (i.e., held at a constant level via experimenter-controlled infusions) at, below, or above subjects' self-determined drug satiety thresholds.
Results
USVs indicated that (1) positive affect was predominantly observed during the drug loading period, but declined quickly to near zero during maintenance and exhibited little relation to calculated drug level, and (2) in contrast, negative affect was observed at sub-satiety cocaine levels, but was relatively absent when body levels of cocaine were clamped at or above subjects' satiety thresholds.
Conclusions
The results reinforce the opponent-process hypothesis of addiction and suggest that an understanding of the mechanisms underlying negative affect might serve to inform behavioral and pharmacological therapies.
References
[NIDA] National Institute on Drug Abuse (US) (1985) Cocaine use in America: Epidemiologic and clinical perspectives. Research monograph series. Department of Health and Human Services (US), Rockville, DHHS Pub. No. (ADM) 90–1414
Ahrens AM, Ma ST, Maier EY, Duvauchelle CL, Shallert T (2009) Repeated intravenous amphetamine exposure: rapid and persistent of 50-kHz. Behav Brain Res 197:205–209
Barker DJ, Root DH, Ma S, Jha S, Megehee L, Pawlak AP, West MO (2010) Dose-dependent differences in short ultrasonic vocalizations emitted by rats during cocaine self-administration. Psychopharmacology (Berl) 211:435–442
Barker DJ, Bercovicz D, Servilio LC, Simmons SJ, Ma S, Root DH, Pawlak AP, West MO (2013) Rat ultrasonic vocalizations demonstrate that the motivation to contextually reinstate cocaine-seeking behavior does not necessarily involve a hedonic response. Addict Biol. doi:10.1111/adb.12044
Barros HMT, Miczek KA (1996) Withdrawal from oral cocaine in rats: ultrasonic vocalizations and tactile startle. Psychopharmacology (Berl) 125:379–384
Breiter HC, Gollub RL, Weisskoff RM, Kennedy DN, Makris N, Berke JD et al (1997) Acute effects of cocaine on human brain activity and emotion. Neuron 19(3):591–611
Browning JR, Browning DA, Maxwell AO, Dong Y, Jansen HT, Panksepp J, Sorg BA (2011) Positive affective vocalizations during cocaine and sucrose self-administration: a model for spontaneous drug desire in rats. Neuropharmacology 61(1–2):268–275
Brudzynski SM (2008) Communication of adult rats by ultrasonic vocalization: biological, sociobiological, and neuroscience approaches. ILAR J 50:43–50
Brudzynski SM (2013) Ethotransmission: communication of emotional states through ultrasonic vocalizations in rats. Curr Opin Neurobiol 23(3):310–317
Brudzynski SM, Ociepa D, Bihari F (1991) Comparison between cholinergically and naturally induced ultrasonic vocalization in the rat. J Psychiatry Neurosci 16:221–226
Brudzynski SM, Bihari F, Ociepa D, Fu X (1993) Analysis of 22 kHz ultrasonic vocalizations in laboratory rats: long and short calls. Physiol Behav 54:215–221
Coffey KC, Barker DJ, Ma S, Root DH, Martinez L, Horvitz JC, West MO (2013) Effects of varying reinforcement probability on Pavlovian approach behavior and ultrasonic vocalizations in rats. Behav Brain Res 237:256–262
Covington HE III, Miczek KA (2003) Vocalizations during withdrawal from opiates and cocaine: possible expressions of affective distress. Eur J Pharmacol 467:1–13
Dougherty J, Pickens R (1973) Fixed-interval schedules of intravenous cocaine presentation in rats. JEAB 20(1):111–118
Dworkin SI, Mirkis S, Smith JE (1995) Response-dependent versus response-independent presentation of cocaine: differences in the lethal effects of the drug. Psychopharmacology (Berl) 117(3):262–266
Ettenberg A (2004) Opponent process properties of self-administered cocaine. Neurosci Biochem Rev 27(8):721–728
Ettenberg A, Raven MA, Danluck DA, Necessary BB (1999) Evidence for opponent-process actions of intravenous cocaine. Pharmacol Biochem Behav 64(3):507–512
Fox HC, Axelrod SR, Paliwal P, Sleeper J, Sinha R (2007) Difficulties in emotion regulation and impulse control during cocaine abstinence. Drug Alcohol Depend 89:298–301
Grace AA (1995) The tonic/phasic model of dopamine system regulation: its relevance for understanding how stimulant abuse can alter basal ganglia function. Drug Alcohol Depend 37:111–129
Hodgins DC, el-Guebaly N, Armstrong S (1995) Prospective and retrospective reports of mood states before relapse to substance use. J Consult Clin Psychol 63(3):400–407
Jhou TC, Good CH, Rowley CS, Xu S, Wang H, Burnham NW, Hoffman AF, Lupica CR, Ikemoto S (2013) Cocaine drives aversive conditioning via delayed activation of dopamine-responsive habenular and midbrain pathways. J Neurosci 33(17):7501–7512
Koob GF (2008) Hedonic homeostatic dysregulation as a driver of drug seeking behavior. Drug Discov Today Dis Models 5(4):207–215
Koob GF (2009a) Dynamics of neuronal circuits in addiction: reward, antireward and emotional memory. Pharmacopsychiatry 42:S32–S41
Koob GF (2009b) Neurobiological substrates for the dark side of compulsivity in addiction. Neuropharmacology 56:18–31
Levinthal CF (2010) Drugs behavior and modern society. Allyn & Bacon, Boston
Lynch WJ, Carroll ME (2001) Regulation of drug intake. Exp Clin Psychopharmacol 9(2):131–143
Ma ST, Maier EY, Ahrens AM, Schallert T, Duvauchelle C (2010) Repeated intravenous cocaine experience: development and escalation of pre-drug anticipatory 50-kHz ultrasonic vocalizations in rats. Behav Brain Res 212:109–114
Mahler SV, Moorman DE, Feltenstein MW, Cox BM, Ogburn KB, Bachar M, McGonigal JT, Ghee SM, See RE (2013) A rodent "self-report" measure of methamphetamine craving? Ultrasonic vocalizations during methamphetamine self-administration, extinction, and reinstatement. Behav Brain Res 236(1):78–89
Maier EY, Ahrens AM, Ma ST, Schallert T, Duvachelle CL (2010) Cocaine deprivation effect: cue abstinence over weekends boosts anticipatory 50-kHz ultrasonic vocalizations in rats. Behav Brain Res 214(1):75–79
Maier EY, Abdalla M, Ahrens AM, Schallert T, Duvachelle CL (2012) The missing variable: ultrasonic vocalizations reveal hidden sensitization and tolerance-like effects during long-term cocaine administration. Psychopharmacology (Berl) 219(4):1141–1152
Meyer PJ, Ma ST, Robinson TE (2012) A cocaine cue is more preferred and evokes more frequency-modulated 50-kHz ultrasonic vocalizations in rats prone to attribute incentive salience to a food cue. Psychopharmacology (Berl) 219(4):999–1009
Mu P, Fuchs T, Saal DB, Sorg BA, Dong Y, Panksepp J (2009) Repeated cocaine exposure induces sensitization of ultrasonic vocalizations in rats. Neurosci Lett 453:31–35
Mutschler NH, Miczek KA (1998a) Withdrawal from IV cocaine "binges" in rats: ultrasonic distress calls and startle. Psychopharmacology (Berl) 135:161–168
Mutschler NH, Miczek KA (1998b) Withdrawal from a self-administered or non-contingent cocaine binge: differences in ultrasonic distress vocalizations in rats. Psychopharmacology (Berl) 136:402–408
Nader MA, Daunais JB, Moore T, Nader SH, Moore RJ, Smith HR, Friedman DP, Porrino LJ (2002) Effects of cocaine self-administration on striatal dopamine systems in rhesus monkeys: initial and chronic exposure. Neuropsychopharmacology 27(1):35–46
Norman AB, Tsibulsky VL (2006) The compulsion zone: a pharmacological theory of acquired cocaine self-administration. Brain Res 1116:143–152
Olmstead MC, Lafond MV, Everitt BJ, Dickinson A (2000) Cocaine seeking by rats is a goal-directed action. Behav Neurosci 115(2):394–402
Panksepp J, Knutson B, Burgdorf (2002) The role of brain emotional system in addictions: a neuro-evolutionary perspective and new 'self-report' animal model. Addiction 97(4):459–469
Pickens R, Thompson T (1968) Cocaine reinforced behavior in rats: effects of reinforcement magnitude and fixed ratio size. J Pharmacol Exp Ther 161:122–129
Pickens R, Thompson T (1971) Characteristics of stimulant reinforcement. In: Thompson T, Pickens R (eds) Stimulus properties of drugs. Appleton-Century-Crofts, New York, pp 172–192
Root DH, Barker DJ, Ma S, Coffey KR, Fabbricatore AT, West MO (2011) Evidence for learned skill during cocaine self-administration in rats. Psychopharmacology (Berl) 217:91–100
Schank JR, Cameron L, Weinshenker D (2008) Norepinephrine signaling through β-adrenergic receptors is critical for expression of cocaine-induced anxiety. Biol Psychiatry 63(11):1007–1012
Simola N, Ma ST, Schallert T (2010) Influence of acute caffeine on 50-kHz ultrasonic vocalizations in male adult rats and relevance to caffeine-mediated psychopharmacological effects. Int J Neuropsychopharmacol 13(1):123–132
Solomon RL, Corbit JD (1978) An opponent-process theory of motivation. Am Econ Rev 68(6):12–24
Taracha E, Hamed A, Krząścik P, Lehner M, Skórzewska A, Płaźnik A, Chrapusta SJ (2012) Inter-individual diversity and intra-individual stability of amphetamine-induced sensitization of frequency-modulated 50-kHz vocalization in Sprague–Dawley rats. Psychopharmacology (Berl) 222(4):619–632
Thompson B, Leonard KC, Brudzynski SM (2006) Amphetamine-induced 50 kHz calls from rat nucleus accumbens: a quantitative mapping study and acoustic analysis. Behav Brain Res 168:64–73
Tsibulsky VL, Norman AB (1999) Satiety threshold: a quantitative model of maintained cocaine self-administration. Brain Res 839:85–93
Volkow ND, Wang GJ, Fischman MW, Foltin RW, Fowler JS, Abumrad NN et al (1997) Relationship between subjective effects of cocaine and dopamine transporter occupancy. Nature 386:827–830
Wheeler RA, Twining RC, Jones JL, Slater JM, Grigson PS, Carelli RM (2008) Behavioral and electrophysiological indices of negative affect predict cocaine self-administration. Neuron 57:774–785
Wheeler RA, Aragona BJ, Fuhrmann KA, Jones JL, Day JJ, Cacciapaglia F, Wightman RM, Carelli RM (2011) Cocaine cues drive opposing context-dependent shifts in reward processing and emotional state. Biol Psychiatry 69(11):1067–1074
Wise RA (1987) The role of reward pathways in the development of drug dependence. Pharmacol Ther 35(1–2):227–263
Wise RA, Bozarth MA (1987) A psychomotor stimulant theory of addiction. Psychol Rev 94(4):469–492
Wise RA, Newton P, Leeb K, Burnette B, Pocock D, Justice JB Jr (1995) Fluctuations in nucleus accumbens dopamine concentration during intravenous cocaine self-administration in rats. Psychopharmacology (Berl) 120(1):10–20
Wöhr M, Schwarting RW (2007) Ultrasonic communication in rats: can playback of 50-kHz calls induce approach behavior? PLoS ONE 2(12):e1365. doi:10.1371/journal.pone.0001365
Wright JS, Panksepp J (2011) Toward affective circuit-based preclinical models of depression: sensitizing dorsal PAG arousal leads to sustained suppression of positive affect in rats. Neurosci Biobehav Rev 35:1902–1915
Wright JM, Gourdon JC, Clarke PBS (2010) Identification of multiple call categories within the rich repertoire of adult rat 50-kHz ultrasonic vocalizations: effects of amphetamine and social context. Psychopharmacology (Berl) 211(1):1–13
Wright JM, Deng L, Clarke PBS (2012) Failure of rewarding and locomotor stimulant doses of morphine to promote rat 50-kHz ultrasonic vocalizations. Psychopharmacology (Berl). doi:10.1007/s00213-012-2776-z
Yokel AR, Pickens R (1974) Drug level of d- and l-amphetamine during intravenous self-administration. Psychopharmacologia 34:255–264
Zimmer BA, Dobrin CV, Roberts DCS (2013) Examination of behavioral strategies regulating cocaine intake in rats. Psychopharmacology (Berl) 225(4):935–944
Acknowledgments
We thank Thomas Grace Sr., Jackie Thomas, and Kevin Coffey for excellent assistance. This study was supported by the National Institute on Drug Abuse Grants DA006886 (MOW), DA029873 (MOW), and DA032270 (DJB).
Conflict of interest
The authors have no financial interests to be disclosed. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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This article is dedicated to the memory of Linda King, a colleague whose character and commitment to students will not be forgotten.
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Barker, D.J., Simmons, S.J., Servilio, L.C. et al. Ultrasonic vocalizations: evidence for an affective opponent process during cocaine self-administration. Psychopharmacology 231, 909–918 (2014). https://doi.org/10.1007/s00213-013-3309-0
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DOI: https://doi.org/10.1007/s00213-013-3309-0