3. =
• Synthetic cathinones are a novel group of psychostimulant
compounds gaining popularity worldwide as “legal high”
alternatives to scheduled drugs
• Beta-ketone amphetamines
• Synthetic cathinone abuse has risen exponentially since
entering the US around 2003
• Available in head shops and internet sites, often
misrepresented as non-consumable products (ie. Bath
salts, plant cleaner, various detergents)
4. • Triple monoamine transporter
reuptake inhibitor (Baumann et al., 2013)
• Preferential activity at DAT and NET over
SERT
• 10x fold potency compared to cocaine
• Self-administered by rats
(Aarde et al., 2013 and 2015, Baumann et al., 2013)
To date, no studies have been
evaluated effects of MDPV on the
glutamate system
MDPV Structure
Prosser et al., 2012 J Med Toxicology
5. • Glutamate transporter
subtype-1 (GLT-1)
• Can be activated
pharmacologically by
ceftriaxone (CEF) and N-
acetylcysteine (NAC)
• GLT-1 activators CEF and
NAC attenuate cocaine
sensitization, reward and
reinforcement (Sari et al., 2009,
Knackstedt et al., 2010, Amen et al., 2011)
Will we observe similar effects of GLT-1
activation on MDPV?
Kalivas et al., 2009 Nature Reviews
6. • Saline or CEF (200 mg/kg
IP) were administered
during the development
of sensitization
• CEF attenuated
sensitization of MDPV
stereotypy compared to
repeated MDPV
Group Name Pre-Conditioning Conditioning Phase Withdrawal Phase Challenge Day
Days 1-4 Days 5-11 Days 21 Day 22
Saline Saline Saline No treatment Saline
Acute MDPV Saline Saline No treatment 0.5 mg/kg MDPV
Repeated MDPV Saline Variable dose MDPV No treatment 0.5 mg/kg MDPV
Repeated Cef +
MDPV
CEF (200 mg/kg) IP
CEF (200 mg/kg) 30
minutes prior to
Variable-dose MDPV
No treatment 0.5 mg/kg MDPV
7-day Variable Dose
Design:
• Days 1 + 7- 0.5 mg/kg
MDPV
• Days 2-6- 1.0 mg/kg
MDPV
7. • Conditioned place preference (CPP) is a
non-operant conditioning method for
measuring the rewarding properties of a
drug
• Drug of interest administered prior to
confinement in non-preferred
compartment
• 4 days of conditioning, 30 minute
sessions
Group Name Pre-Conditioning Pre-test Conditioning Phase Post-test
n=7-9/group Days 1-3 Day 4 Day 5-8 Day 9
Saline + Saline Saline Saline Saline in both compartments No treatment
CEF + Saline CEF (200 mg/kg) IP
CEF (200 mg/kg) 30 minutes
prior to pre-test
CEF (200 mg/kg) 30 minutes prior to non-
preferred side
No treatment
Saline + MDPV Saline Saline
MDPV (2.0 mg/kg, IP) immediately prior
to non-preferred side
No treatment
CEF + MDPV CEF (200 mg/kg) IP
CEF (200 mg/kg) 30 minutes
prior to pre-test
CEF 30 minutes prior to MDPV (2.0 mg/kg,
IP) immediately prior to non-preferred
side
No treatment
8. • MDPV produces a preference shift after 4
days of conditioning
• CEF attenuated MDPV place preference
when administered during development
• Activation of GLT-1 by CEF treatment
attenuates the rewarding properties of
MDPV.
Will we observe similar
effects in relapse models?
9. • Gold standard for determining abuse
liability of drugs and susceptibility to
relapse
• Self-administration criteria:
• 0.056 mg/kg/infusion MDPV
• 2 hour sessions
• 2 days FR1 sucrose
• 14 days FR1 MDPV
• 10 days of extinction training
• Cue- and cue+drug reinstatement tests
Group Name Acquisition Extinction Cue-Reinstatement Cue + Drug Reinstatement
n=7-9/group Days 1-14 Days 15-24 Day 25 Day 26
Saline
MDPV (0.056
mg/kg/infusion)
Saline prior to
extinction
session
No drug. Cue light and
sounds are active
0.5 mg/kg MDPV immediately before session. Cue lights
and sounds are active
Ceftriaxone
MDPV (0.056
mg/kg/infusion)
CEF (200 mg/kg)
30 minutes prior
to extinction
session
No drug. Cue light and
sounds are active
0.5 mg/kg MDPV immediately before session. Cue lights
and sounds are active
N-acetylcysteine
MDPV (0.056
mg/kg/infusion)
N-acetylcysteine
(100 mg/kg) 30
minutes prior to
extinction
session
No drug. Cue light and
sounds are active
0.5 mg/kg MDPV immediately before session. Cue lights
and sounds are active
10.
11. • CEF attenuates development of MDPV
behavioral sensitization and reward in non-
contingent administration assays
• Neither CEF nor NAC attenuates reinstatement
of MDPV drug seeking in operant self-
administration assays
• CEF and NAC block development and
expression of cocaine reinstatement in
similar paradigms (Knackstedt et al., 2010,
Reichel et al., 2011)
• CEF effects on MDPV reinstatement may
be specific to specific phases in the
addiction cycle (ie. development vs.
expression)
• Future studies will investigate CEF
and NAC against the development of
MDPV reinstatement of drug seeking
12. Rawls Lab
• Scott Rawls, PhD
• Lucas Watterson, PhD
• Chris Tallarida
• Jae Kim
• Helene Philogene
Funding Sources
• NIDA DA013429
• NIDA DA033270
