During the previous funding period, individual memory systems were evaluated for their role in regulating associative learning processes studied in an eight-arm radial maze as well as in regulating behavior studied in a self-administration maintenance/reinstatement model in rats. The results generated specific hypotheses to suggest (1) that the rostral and caudal subregions of basolateral amygdala are functionally heterogeneous and may therefore have a differential sensitivity to dopamine agonists and antagonists for modifying drug-seeking under maintenance and reinstatement conditions; (2) that the lateral dorsal striatum may regulate the dose-related effects of self-administered cocaine; (3) that the hippocampal subicular subregions may regulate drug-seeking behavior during the contextual encoding (acquisition) stage, but not after contextual information is consolidated; and (4) that within session changes in DA neurotransmission in the lateral prefrontal cortex may regulate the within session changes in the pattern of drug-seeking behavior normally observed.
Specific aim 1 will test these four hypotheses.
For specific aim 2, the interactions between memory systems that are interconnected within two parallel corticostriatalpallidothalamic circuits as well as within the corticostriatalpallido-subthalamic circuit (interface between the basal ganglia and limbic system) will be explored. Specific hypotheses to be tested will be guided by conducting simulations with our newly developed neurocomputational model of drug-seeking behavior. In in vivo experiments, Fos protein expression in the nucleus accumbens at different phases of the cocaine addiction process will be measured in conjunction with the asymmetric GABA agonist inactivation technique to help elucidate if components of these different circuits work cooperatively, competitively or independently in regulating addiction-related behavior. The completion of these aims will advance our understanding of how neurocognitive substrates may regulate drug use and relapse. By studying memory system functions and their interactions during different phases of the cocaine addiction process, insight into the complex challenges that face successful treatment of cocaine-addicted individuals will surface and perhaps guide medications development.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA011716-09
Application #
7252456
Study Section
Neurobiology of Motivated Behavior Study Section (NMB)
Program Officer
Aigner, Thomas G
Project Start
1998-04-20
Project End
2009-06-30
Budget Start
2007-07-01
Budget End
2008-06-30
Support Year
9
Fiscal Year
2007
Total Cost
$306,262
Indirect Cost
Name
Boston University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
049435266
City
Boston
State
MA
Country
United States
Zip Code
02215
Baskin, Britahny M; Nic Dhonnchadha, Bríd Á; Dwoskin, Linda P et al. (2017) Blockade of ?2-adrenergic receptors in prelimbic cortex: impact on cocaine self-administration in adult spontaneously hypertensive rats following adolescent atomoxetine treatment. Psychopharmacology (Berl) 234:2897-2909
Kantak, Kathleen M; Dwoskin, Linda P (2016) Necessity for research directed at stimulant type and treatment-onset age to access the impact of medication on drug abuse vulnerability in teenagers with ADHD. Pharmacol Biochem Behav 145:24-6
Somkuwar, S S; Kantak, K M; Bardo, M T et al. (2016) Adolescent methylphenidate treatment differentially alters adult impulsivity and hyperactivity in the Spontaneously Hypertensive Rat model of ADHD. Pharmacol Biochem Behav 141:66-77
Jordan, Chloe J; Lemay, Carley; Dwoskin, Linda P et al. (2016) Adolescent d-amphetamine treatment in a rodent model of attention deficit/hyperactivity disorder: impact on cocaine abuse vulnerability in adulthood. Psychopharmacology (Berl) 233:3891-3903
Jordan, Chloe J; Taylor, Danielle M; Dwoskin, Linda P et al. (2016) Adolescent D-amphetamine treatment in a rodent model of ADHD: Pro-cognitive effects in adolescence without an impact on cocaine cue reactivity in adulthood. Behav Brain Res 297:165-79
Baskin, Britahny M; Dwoskin, Linda P; Kantak, Kathleen M (2015) Methylphenidate treatment beyond adolescence maintains increased cocaine self-administration in the spontaneously hypertensive rat model of attention deficit/hyperactivity disorder. Pharmacol Biochem Behav 131:51-6
Somkuwar, Sucharita S; Kantak, Kathleen M; Dwoskin, Linda P (2015) Effect of methylphenidate treatment during adolescence on norepinephrine transporter function in orbitofrontal cortex in a rat model of attention deficit hyperactivity disorder. J Neurosci Methods 252:55-63
Kantak, Kathleen M; Barlow, Nicole; Tassin, David H et al. (2014) Performance on a strategy set shifting task in rats following adult or adolescent cocaine exposure. Psychopharmacology (Berl) 231:4489-501
Jordan, Chloe J; Harvey, Roxann C; Baskin, Britahny B et al. (2014) Cocaine-seeking behavior in a genetic model of attention-deficit/hyperactivity disorder following adolescent methylphenidate or atomoxetine treatments. Drug Alcohol Depend 140:25-32
Gauthier, Jamie M; Tassin, David H; Dwoskin, Linda P et al. (2014) Effects of dopamine D1 receptor blockade in the prelimbic prefrontal cortex or lateral dorsal striatum on frontostriatal function in Wistar and Spontaneously Hypertensive Rats. Behav Brain Res 268:229-38

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